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Department of Medicine, University of Szeged, Szeged, 6720, Hungary
HAS-USZ Momentum Epithelial Cell Signaling and Secretion Research Group, University of Szeged, Szeged, 6720, Hungary
First Department of Pediatrics, Semmelweis University, Budapest, Hungary
Department of Pathophysiology, University of Szeged, Szeged, 6720, Hungary
Department of Pathology, University of Szeged, Szeged, Hungary
Department of Internal Medicine I, Ulm University Hospital, Ulm, Germany
Biosciences Institute, Newcastle University, Newcastle upon Tyne, United Kingdom
Institute for Translational Medicine, University of Pécs, Pécs, Hungary
Centre for Translational Medicine and Division for Pancreatic Disorders, Semmelweis University, Budapest, Hungary
HCEMM-USZ Molecular Gastroenterology Research Group, University of Szeged, Szeged, 6720, Hungary
Cited By :4
Export Date: 26 January 2024
CODEN: CMLSF
Correspondence Address: Maléth, J.; Department of Medicine, Hungary; email: jozsefmaleth1@gmail.com
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Impaired regulation of PMCA activity by defective CFTR expression promotes epithelial cell damage in alcoholic pancreatitis and hepatitis.
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Alcoholic pancreatitis and hepatitis are frequent, potentially lethal diseases with limited treatment options. Our previous study reported that the expression of CFTR Cl- channel is impaired by ethanol in pancreatic ductal cells leading to more severe alcohol-induced pancreatitis. In addition to determining epithelial ion secretion, CFTR has multiple interactions with other proteins, which may influence intracellular Ca2+ signaling. Thus, we aimed to investigate the impact of ethanol-mediated CFTR damage on intracellular Ca2+ homeostasis in pancreatic ductal epithelial cells and cholangiocytes. Human and mouse pancreas and liver samples and organoids were used to study ion secretion, intracellular signaling, protein expression and interaction. The effect of PMCA4 inhibition was analyzed in a mouse model of alcohol-induced pancreatitis. The decreased CFTR expression impaired PMCA function and resulted in sustained intracellular Ca2+ elevation in ethanol-treated and mouse and human pancreatic organoids. Liver samples derived from alcoholic hepatitis patients and ethanol-treated mouse liver organoids showed decreased CFTR expression and function, and impaired PMCA4 activity. PMCA4 co-localizes and physically interacts with CFTR on the apical membrane of polarized epithelial cells, where CFTR-dependent calmodulin recruitment determines PMCA4 activity. The sustained intracellular Ca2+ elevation in the absence of CFTR inhibited mitochondrial function and was accompanied with increased apoptosis in pancreatic epithelial cells and PMCA4 inhibition increased the severity of alcohol-induced AP in mice. Our results suggest that improving Ca2+ extrusion in epithelial cells may be a potential novel therapeutic approach to protect the exocrine pancreatic function in alcoholic pancreatitis and prevent the development of cholestasis in alcoholic hepatitis.
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<div class="JournalArticle Publication short-list"> <div class="authors"> <span class="author-name" mtid="10059215"> <a href="/gui2/?type=authors&mode=browse&sel=10059215" target="_blank">Madácsy, Tamara</a> </span> <span class="author-type"> </span> ; <span class="author-name" mtid="10061075"> <a href="/gui2/?type=authors&mode=browse&sel=10061075" target="_blank">Varga, Árpád</a> </span> <span class="author-type"> </span> ; <span class="author-name" mtid="10073859"> <a href="/gui2/?type=authors&mode=browse&sel=10073859" target="_blank">Papp, Noémi</a> </span> <span class="author-type"> </span> ; <span class="author-name" mtid="10061191"> <a href="/gui2/?type=authors&mode=browse&sel=10061191" target="_blank">Tél, Bálint</a> </span> <span class="author-type"> </span> ; <span class="author-name" mtid="10030075"> <a href="/gui2/?type=authors&mode=browse&sel=10030075" target="_blank">Pallagi, Petra</a> </span> <span class="author-type"> </span> ; <span class="author-name" mtid="10050549"> <a href="/gui2/?type=authors&mode=browse&sel=10050549" target="_blank">Szabó, Viktória</a> </span> <span class="author-type"> </span> ; <span class="author-name" mtid="10078338"> <a href="/gui2/?type=authors&mode=browse&sel=10078338" target="_blank">Kiss, Aletta</a> </span> <span class="author-type"> </span> ; <span class="author-name" mtid="10054985"> <a href="/gui2/?type=authors&mode=browse&sel=10054985" target="_blank">Fanczal, Júlia</a> </span> <span class="author-type"> </span> ; <span class="author-name" mtid="10000098"> <a href="/gui2/?type=authors&mode=browse&sel=10000098" target="_blank">Rakonczay, Zoltan</a> </span> <span class="author-type"> </span> ; <span class="author-name" mtid="10009640"> <a href="/gui2/?type=authors&mode=browse&sel=10009640" target="_blank">Tiszlavicz, László</a> </span> <span class="author-type"> </span> et al. </div ><div class="title"><a href="/gui2/?mode=browse¶ms=publication;32800045" mtid="32800045" target="_blank">Impaired regulation of PMCA activity by defective CFTR expression promotes epithelial cell damage in alcoholic pancreatitis and hepatitis.</a></div> <div class="pub-info"> <span class="journal-title">CELLULAR AND MOLECULAR LIFE SCIENCES</span> <span class="journal-volume">79</span> : <span class="journal-issue">5</span> <span class="page"> Paper: 265 , 18 p. </span> <span class="year">(2022)</span> </div> <div class="pub-end"><div class="identifier-list"> <span class="identifiers"> <span class="id identifier oa_PAY" title=" Fizetős "> <a style="color:blue" title="10.1007/s00018-022-04287-1" target="_blank" href="https://doi.org/10.1007/s00018-022-04287-1"> DOI </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="000788589900002" target="_blank" href="https://www.webofscience.com/wos/woscc/full-record/000788589900002"> WoS </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="85128911865" target="_blank" href="http://www.scopus.com/record/display.url?origin=inward&eid=2-s2.0-85128911865"> Scopus </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="35484438" target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=35484438&dopt=Abstract"> PubMed </a> </span> <span class="id identifier oa_GREEN" title=" Green "> <a style="color:blue" title="24664" target="_blank" href="http://publicatio.bibl.u-szeged.hu/24664"> SZTE Publicatio </a> </span> </span> </div> <div class="short-pub-prop-list"> <span class="short-pub-mtid"> Közlemény:32800045 </span> <span class="status-holder"><span class="status-data status-VALIDATED"> Egyeztetett </span></span> <span class="pub-core">Forrás Idéző </span> <span class="pub-type">Folyóiratcikk (Szakcikk ) </span> <!-- && !record.category.scientific --> <span class="pub-category">Tudományos</span> <div class="publication-citation" style="margin-left: 0.5cm;"> <span title="Nyilvános idézőközlemények összesen, említések nélkül" class="citingPub-count">Nyilvános idéző összesen: 6</span> | Független: 3 | Függő: 3 | Nem jelölt: 0 | WoS jelölt: 5 | Scopus jelölt: 5 | WoS/Scopus jelölt: 5 | DOI jelölt: 5 </div> </div> </div> </div><div class="JournalArticle Publication long-list">
<div class="authors">
<img title="Forrásközlemény" style="float: left" src="/frontend/resources/grid/publication-core-icon.png">
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<div class="autype autype0"> <span class="author-name" mtid="10059215"><a
href="/gui2/?type=authors&mode=browse&sel=10059215" target="_blank">Madácsy Tamara
(<span class="authorship-author-name">Madácsy Tamara</span>
<span class="authorAux-mtmt"> sejtélettan</span>)
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<span class="author-affil"><span title="Szegedi Tudományegyetem">SZTE</span>/<span title="Szent-Györgyi Albert Orvostudományi Kar">SZAOK</span>/<span title="Belgyógyászati Klinika">BK</span>/I. sz. Belgyógyászati Klinika; <span title="Szegedi Tudományegyetem">SZTE</span>/<span title="Szent-Györgyi Albert Orvostudományi Kar">SZAOK</span>/<span title="Belgyógyászati Klinika">BK</span>/<span title="I. sz. Belgyógyászati Klinika">I.BelK</span>/MTA-SZTE Lendület Epitél Sejt Szignalizáció és Szekréció Kutatócsoport</span>
;
<span class="author-name" mtid="10061075"><a
href="/gui2/?type=authors&mode=browse&sel=10061075" target="_blank">Varga Árpád
(<span class="authorship-author-name">Varga Árpád</span>
<span class="authorAux-mtmt"> Sejt- és molekuláris biológia</span>)
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</span>
<span class="author-affil"><span title="Szegedi Tudományegyetem">SZTE</span>/<span title="Szent-Györgyi Albert Orvostudományi Kar">SZAOK</span>/<span title="Belgyógyászati Klinika">BK</span>/I. sz. Belgyógyászati Klinika; <span title="Szegedi Tudományegyetem">SZTE</span>/<span title="Szent-Györgyi Albert Orvostudományi Kar">SZAOK</span>/<span title="Belgyógyászati Klinika">BK</span>/<span title="I. sz. Belgyógyászati Klinika">I.BelK</span>/MTA-SZTE Lendület Epitél Sejt Szignalizáció és Szekréció Kutatócsoport</span>
;
<span class="author-name" mtid="10073859"><a
href="/gui2/?type=authors&mode=browse&sel=10073859" target="_blank">Papp Noémi
(<span class="authorship-author-name">Csákány-Papp Noémi</span>
<span class="authorAux-mtmt"> Gasztroenterológia</span>)
</a>
</span>
<span class="author-affil"><span title="Szegedi Tudományegyetem">SZTE</span>/<span title="Szent-Györgyi Albert Orvostudományi Kar">SZAOK</span>/<span title="Belgyógyászati Klinika">BK</span>/I. sz. Belgyógyászati Klinika; <span title="Szegedi Tudományegyetem">SZTE</span>/<span title="Szent-Györgyi Albert Orvostudományi Kar">SZAOK</span>/<span title="Belgyógyászati Klinika">BK</span>/<span title="I. sz. Belgyógyászati Klinika">I.BelK</span>/MTA-SZTE Lendület Epitél Sejt Szignalizáció és Szekréció Kutatócsoport</span>
;
<span class="author-name" mtid="10061191"><a
href="/gui2/?type=authors&mode=browse&sel=10061191" target="_blank">Tél Bálint
(<span class="authorship-author-name">Tél Bálint</span>
<span class="authorAux-mtmt"> általános orvostudomány</span>)
</a>
</span>
<span class="author-affil"><span title="Semmelweis Egyetem">SE</span>/<span title="Általános Orvostudományi Kar">AOK</span>/<span title="Klinikum">K</span>/I. Sz. Gyermekgyógyászati Klinika; <span title="Szegedi Tudományegyetem">SZTE</span>/<span title="Szent-Györgyi Albert Orvostudományi Kar">SZAOK</span>/<span title="Belgyógyászati Klinika">BK</span>/<span title="I. sz. Belgyógyászati Klinika">I.BelK</span>/MTA-SZTE Lendület Epitél Sejt Szignalizáció és Szekréció Kutatócsoport</span>
;
<span class="author-name" mtid="10030075"><a
href="/gui2/?type=authors&mode=browse&sel=10030075" target="_blank">Pallagi Petra
(<span class="authorship-author-name">Pallagi Petra</span>
<span class="authorAux-mtmt"> Gasztroenterológia</span>)
</a>
</span>
<span class="author-affil"><span title="Szegedi Tudományegyetem">SZTE</span>/<span title="Szent-Györgyi Albert Orvostudományi Kar">SZAOK</span>/<span title="Belgyógyászati Klinika">BK</span>/I. sz. Belgyógyászati Klinika; <span title="Szegedi Tudományegyetem">SZTE</span>/<span title="Szent-Györgyi Albert Orvostudományi Kar">SZAOK</span>/<span title="Belgyógyászati Klinika">BK</span>/<span title="I. sz. Belgyógyászati Klinika">I.BelK</span>/MTA-SZTE Lendület Epitél Sejt Szignalizáció és Szekréció Kutatócsoport</span>
;
<span class="author-name" mtid="10050549"><a
href="/gui2/?type=authors&mode=browse&sel=10050549" target="_blank">Szabó Viktória
(<span class="authorship-author-name">Szabó Viktória</span>
<span class="authorAux-mtmt"> Genetika</span>)
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<span class="author-affil"><span title="Szegedi Tudományegyetem">SZTE</span>/<span title="Szent-Györgyi Albert Orvostudományi Kar">SZAOK</span>/<span title="Belgyógyászati Klinika">BK</span>/I. sz. Belgyógyászati Klinika; <span title="Szegedi Tudományegyetem">SZTE</span>/<span title="Szent-Györgyi Albert Orvostudományi Kar">SZAOK</span>/<span title="Belgyógyászati Klinika">BK</span>/<span title="I. sz. Belgyógyászati Klinika">I.BelK</span>/MTA-SZTE Lendület Epitél Sejt Szignalizáció és Szekréció Kutatócsoport</span>
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<span class="author-name" mtid="10078338"><a
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<span class="author-affil"><span title="Szegedi Tudományegyetem">SZTE</span>/<span title="Szent-Györgyi Albert Orvostudományi Kar">SZAOK</span>/<span title="Belgyógyászati Klinika">BK</span>/<span title="I. sz. Belgyógyászati Klinika">I.BelK</span>/MTA-SZTE Lendület Epitél Sejt Szignalizáció és Szekréció Kutatócsoport</span>
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<span class="author-name" mtid="10054985"><a
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<span class="authorAux-mtmt"> pancreatitis (alapkutatás)</span>)
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<span class="author-affil"><span title="Szegedi Tudományegyetem">SZTE</span>/<span title="Szent-Györgyi Albert Orvostudományi Kar">SZAOK</span>/<span title="Belgyógyászati Klinika">BK</span>/I. sz. Belgyógyászati Klinika; <span title="Szegedi Tudományegyetem">SZTE</span>/<span title="Szent-Györgyi Albert Orvostudományi Kar">SZAOK</span>/<span title="Belgyógyászati Klinika">BK</span>/<span title="I. sz. Belgyógyászati Klinika">I.BelK</span>/MTA-SZTE Lendület Epitél Sejt Szignalizáció és Szekréció Kutatócsoport</span>
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<span class="author-name" mtid="10000098"><a
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<span class="authorAux-mtmt"> Gasztroenterológia</span>)
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<span class="author-affil"><span title="Szegedi Tudományegyetem">SZTE</span>/<span title="Szent-Györgyi Albert Orvostudományi Kar">SZAOK</span>/Kórélettani Intézet</span>
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<span class="author-affil"><span title="Szegedi Tudományegyetem">SZTE</span>/<span title="Szent-Györgyi Albert Orvostudományi Kar">SZAOK</span>/Pathológiai Intézet</span>
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<span class="author-name" mtid="10023650"><a
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<span class="author-affil"><span title="Szegedi Tudományegyetem">SZTE</span>/<span title="Szent-Györgyi Albert Orvostudományi Kar">SZAOK</span>/Pathológiai Intézet</span>
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<span class="author-name" >Hohwieler Meike
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<span class="author-name" >Kleger Alexander
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<span class="author-name" >Gray Mike
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<span class="author-name" mtid="10002629"><a
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<span class="author-affil"><span title="Semmelweis Egyetem">SE</span>/<span title="Általános Orvostudományi Kar">AOK</span>/<span title="Klinikum">K</span>/Városmajori Szív- és Érgyógyászati Klinika; <span title="Pécsi Tudományegyetem">PTE</span>/<span title="Általános Orvostudományi Kar">ÁOK</span>/Transzlációs Medicina Intézet; <span title="Semmelweis Egyetem">SE</span>/<span title="Központi Szervezeti Egységek (beleértve az Egyéb Szervezeti Egységeket)">KSZE</span>/Transzlációs Medicina Központ; <span title="Semmelweis Egyetem">SE</span>/<span title="Általános Orvostudományi Kar">AOK</span>/<span title="Klinikum">K</span>/<span title="Városmajori Szív- és Érgyógyászati Klinika">VAROSMAJOR_SZÍVÉRGYÓGY</span>/Pankreász Betegségek Részlege</span>
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<span class="author-affil"><span title="Szegedi Tudományegyetem">SZTE</span>/<span title="Szent-Györgyi Albert Orvostudományi Kar">SZAOK</span>/<span title="Belgyógyászati Klinika">BK</span>/I. sz. Belgyógyászati Klinika; <span title="Szegedi Tudományegyetem">SZTE</span>/<span title="Szent-Györgyi Albert Orvostudományi Kar">SZAOK</span>/<span title="Belgyógyászati Klinika">BK</span>/<span title="I. sz. Belgyógyászati Klinika">I.BelK</span>/MTA-SZTE Lendület Gasztroenterológiai Multidiszciplináris Kutatócsoport; <span title="Szegedi Tudományegyetem">SZTE</span>/<span title="Szent-Györgyi Albert Orvostudományi Kar">SZAOK</span>/<span title="Belgyógyászati Klinika">BK</span>/<span title="I. sz. Belgyógyászati Klinika">I.BelK</span>/MTA-SZTE Lendület Epitél Sejt Szignalizáció és Szekréció Kutatócsoport</span>
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<div class="title"><a href="/gui2/?mode=browse¶ms=publication;32800045" target="_blank">Impaired regulation of PMCA activity by defective CFTR expression promotes epithelial cell damage in alcoholic pancreatitis and hepatitis.</a></div> <div> <span class="journal-title">CELLULAR AND MOLECULAR LIFE SCIENCES</span>
<span class="journal-issn">(<a target="_blank" href="https://portal.issn.org/resource/ISSN/1420-682X">1420-682X</a> <a target="_blank" href="https://portal.issn.org/resource/ISSN/1420-9071">1420-9071</a>)</span>:
<span class="journal-volume">79</span> <span class="journal-issue">5</span>
<span class="page">
Paper 265.
18 p.
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Forrás Idéző
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<div class="funder"> GINOP - STAY ALIVE(GINOP-2.3.2-15-2016-00048) Támogató: Nemzeti Kutatási, Fejlesztési és Innovációs Hivatal, (PD116553), EMBERI ERŐFORRÁS FEJLESZTÉSI OPERATÍV PROGRAM (EFOP)(EFOP-3.6.2-162017-00006) Támogató: NKFIH, (BO/00569/17) Támogató: MTA Bolyai pályázat, (LP2017–18/2017) Támogató: MTA, Smart rendszerek. Új Nemzeti Kiválóság Program(20391-3/2018/FEKUSTRAT) Támogató: EMMI, (TUDFO/47138-1/2019/ITM), Tématerületi Kiválósági Program 2021 - Transzlációs biomedicina(TKP2021-EGA-28) Támogató: NKFIH, Új Nemzeti Kiválóság Program(UNKP-21-4-SZTE-116) Támogató: Nemzeti Kutatás, Fejlesztés és Innovációs Iroda, (ÚNKP-21-3-SZTE-68), Albert Szent-Györgyi Research Grant(5S 470 (A202)), Establishing the Hungarian Center of Excellence for Molecular Medicine in partnership with EMBL(739593) Támogató: Horizon 2020, (NTP-NFTÖ-B-0011), (NTP-NFTÖ-21-B-0205), (NTP-NFTÖ-21-B-0079) </div>
<div class="lastModified">Utolsó módosítás: 2023.06.30. 05:32 Bernátskyné Babus Csilla (SZTE admin4)
</div>
<pre class="comment" style="margin-top: 0; margin-bottom: 0;"><u>Megjegyzés</u>: Department of Medicine, University of Szeged, Szeged, 6720, Hungary
HAS-USZ Momentum Epithelial Cell Signaling and Secretion Research Group, University of Szeged, Szeged, 6720, Hungary
First Department of Pediatrics, Semmelweis University, Budapest, Hungary
Department of Pathophysiology, University of Szeged, Szeged, 6720, ...</pre>
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Sustained intracellular Ca2+ overload in pancreatic acinar and ductal cells is a hallmark of biliary and alcohol-induced acute pancreatitis, which leads to impaired ductal ion and fluid secretion. Orai1 is a plasma membrane Ca2+ channel that mediates extracellular Ca2+ influx upon endoplasmic reticulum Ca2+ depletion. Our results showed that Orai1 is expressed on the luminal plasma membrane of the ductal cells and selective Orai1 inhibition impaired Stim1-dependent extracellular Ca2+ influx evoked by bile acids or ethanol combined with non-oxidative ethanol metabolites. The prevention of sustained extracellular Ca2+ influx protected ductal cell secretory functions in in vitro models and maintained exocrine pancreatic secretion in in vivo AP models. Orai1 inhibition prevents the bile acid-, and alcohol-induced damage of the pancreatic ductal secretion and holds the potential of improving the outcome of acute pancreatitis.Regardless of its etiology, sustained intracellular Ca2+ overload is a well-known hallmark of acute pancreatitis (AP). Toxic Ca2+ elevation induces pancreatic ductal cell damage characterized by impaired ion- and fluid secretion -essential to wash out the protein-rich fluid secreted by acinar cells while maintaining the alkaline intra-ductal pH under physiological conditions- and mitochondrial dysfunction. While prevention of ductal cell injury decreases the severity of AP, no specific drug target has yet been identified in the ductal cells. Although Orai1 -a store operated Ca2+ influx channel- is known to contribute to sustained Ca2+ overload in acinar cells, details concerning its expression and function in ductal cells are currently lacking. In this study, we demonstrate that functionally active Orai1 channels reside dominantly in the apical plasma membrane of pancreatic ductal cells. Selective CM5480-mediated Orai1 inhibition impairs Stim1-dependent extracellular Ca2+ influx evoked by bile acids or ethanol combined with non-oxidative ethanol metabolites. Furthermore, prevention of sustained extracellular Ca2+ influx protects ductal cell secretory function in vitro and decrease pancreatic ductal cell death. Finally, Orai1-inhibition partially restores and maintains proper exocrine pancreatic secretion in in vivo AP models. In conclusion, our results indicate that Orai1 inhibition prevents AP-related ductal cell function impairment and holds the potential of improving disease outcome. Abstract figure legend This article is protected by copyright. All rights reserved.
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<div class="JournalArticle Publication short-list"> <div class="authors"> <span class="author-name" mtid="10030075"> <a href="/gui2/?type=authors&mode=browse&sel=10030075" target="_blank">Pallagi, Petra</a> </span> <span class="author-type"> </span> ; <span class="author-name" mtid="10080809"> <a href="/gui2/?type=authors&mode=browse&sel=10080809" target="_blank">Görög, Marietta<sup>*</sup></a> </span> <span class="author-type"> </span> ; <span class="author-name" mtid="10073859"> <a href="/gui2/?type=authors&mode=browse&sel=10073859" target="_blank">Papp, Noémi</a> </span> <span class="author-type"> </span> ; <span class="author-name" mtid="10059215"> <a href="/gui2/?type=authors&mode=browse&sel=10059215" target="_blank">Madácsy, Tamara</a> </span> <span class="author-type"> </span> ; <span class="author-name" mtid="10061075"> <a href="/gui2/?type=authors&mode=browse&sel=10061075" target="_blank">Varga, Árpád</a> </span> <span class="author-type"> </span> ; <span class="author-name" mtid="10027886"> <a href="/gui2/?type=authors&mode=browse&sel=10027886" target="_blank">Crul, Tim</a> </span> <span class="author-type"> </span> ; <span class="author-name" mtid="10050549"> <a href="/gui2/?type=authors&mode=browse&sel=10050549" target="_blank">Szabó, Viktória</a> </span> <span class="author-type"> </span> ; <span class="author-name" > Molnár, Melinda </span> <span class="author-type"> </span> ; <span class="author-name" mtid="10088774"> <a href="/gui2/?type=authors&mode=browse&sel=10088774" target="_blank">Dudás, Krisztina</a> </span> <span class="author-type"> </span> ; <span class="author-name" > Grassalkovich, Anna </span> <span class="author-type"> </span> et al. </div ><div class="title"><a href="/gui2/?mode=browse¶ms=publication;32624114" mtid="32624114" target="_blank">Bile acid- and ethanol-mediated activation of Orai1 damages pancreatic ductal secretion in acute pancreatitis</a></div> <div class="pub-info"> <span class="journal-title">JOURNAL OF PHYSIOLOGY-LONDON</span> <span class="journal-volume">600</span> : <span class="journal-issue">7</span> <span class="page"> pp. 1631-1650. , 20 p. </span> <span class="year">(2022)</span> </div> <div class="pub-end"><div class="identifier-list"> <span class="identifiers"> <span class="id identifier oa_PAY" title=" Fizetős "> <a style="color:blue" title="10.1113/JP282203" target="_blank" href="https://doi.org/10.1113/JP282203"> DOI </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="000756870200001" target="_blank" href="https://www.webofscience.com/wos/woscc/full-record/000756870200001"> WoS </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="85124729174" target="_blank" href="http://www.scopus.com/record/display.url?origin=inward&eid=2-s2.0-85124729174"> Scopus </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="35081662" target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=35081662&dopt=Abstract"> PubMed </a> </span> <span class="id identifier oa_GREEN" title=" Green "> <a style="color:blue" title="23447" target="_blank" href="http://publicatio.bibl.u-szeged.hu/23447"> SZTE Publicatio </a> </span> </span> </div> <div class="short-pub-prop-list"> <span class="short-pub-mtid"> Közlemény:32624114 </span> <span class="status-holder"><span class="status-data status-VALIDATED"> Egyeztetett </span></span> <span class="pub-core">Forrás Idéző </span> <span class="pub-type">Folyóiratcikk (Szakcikk ) </span> <!-- && !record.category.scientific --> <span class="pub-category">Tudományos</span> <div class="publication-citation" style="margin-left: 0.5cm;"> <span title="Nyilvános idézőközlemények összesen, említések nélkül" class="citingPub-count">Nyilvános idéző összesen: 11</span> | Független: 7 | Függő: 4 | Nem jelölt: 0 | WoS jelölt: 10 | Scopus jelölt: 11 | WoS/Scopus jelölt: 11 | DOI jelölt: 11 </div> </div> </div> </div><div class="JournalArticle Publication long-list">
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<div class="autype autype0"> <span class="author-name" mtid="10030075"><a
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<span class="authorAux-mtmt"> Gasztroenterológia</span>)
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<span class="author-affil"><span title="Szegedi Tudományegyetem">SZTE</span>/<span title="Szent-Györgyi Albert Orvostudományi Kar">SZAOK</span>/<span title="Belgyógyászati Klinika">BK</span>/I. sz. Belgyógyászati Klinika; <span title="Szegedi Tudományegyetem">SZTE</span>/<span title="Szent-Györgyi Albert Orvostudományi Kar">SZAOK</span>/<span title="Belgyógyászati Klinika">BK</span>/<span title="I. sz. Belgyógyászati Klinika">I.BelK</span>/MTA-SZTE Lendület Epitél Sejt Szignalizáció és Szekréció Kutatócsoport</span>
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<span class="author-name" mtid="10080809"><a
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<span class="author-affil"><span title="Szegedi Tudományegyetem">SZTE</span>/<span title="Szent-Györgyi Albert Orvostudományi Kar">SZAOK</span>/<span title="Belgyógyászati Klinika">BK</span>/I. sz. Belgyógyászati Klinika; <span title="Szegedi Tudományegyetem">SZTE</span>/<span title="Szent-Györgyi Albert Orvostudományi Kar">SZAOK</span>/<span title="Belgyógyászati Klinika">BK</span>/<span title="I. sz. Belgyógyászati Klinika">I.BelK</span>/MTA-SZTE Lendület Epitél Sejt Szignalizáció és Szekréció Kutatócsoport</span>
;
<span class="author-name" mtid="10073859"><a
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<span class="authorAux-mtmt"> Gasztroenterológia</span>)
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<span class="author-affil"><span title="Szegedi Tudományegyetem">SZTE</span>/<span title="Szent-Györgyi Albert Orvostudományi Kar">SZAOK</span>/<span title="Belgyógyászati Klinika">BK</span>/I. sz. Belgyógyászati Klinika; <span title="Szegedi Tudományegyetem">SZTE</span>/<span title="Szent-Györgyi Albert Orvostudományi Kar">SZAOK</span>/<span title="Belgyógyászati Klinika">BK</span>/<span title="I. sz. Belgyógyászati Klinika">I.BelK</span>/MTA-SZTE Lendület Epitél Sejt Szignalizáció és Szekréció Kutatócsoport</span>
;
<span class="author-name" mtid="10059215"><a
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<span class="author-affil"><span title="Szegedi Tudományegyetem">SZTE</span>/<span title="Szent-Györgyi Albert Orvostudományi Kar">SZAOK</span>/<span title="Belgyógyászati Klinika">BK</span>/I. sz. Belgyógyászati Klinika; <span title="Szegedi Tudományegyetem">SZTE</span>/<span title="Szent-Györgyi Albert Orvostudományi Kar">SZAOK</span>/<span title="Belgyógyászati Klinika">BK</span>/<span title="I. sz. Belgyógyászati Klinika">I.BelK</span>/MTA-SZTE Lendület Epitél Sejt Szignalizáció és Szekréció Kutatócsoport</span>
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<span class="author-name" mtid="10061075"><a
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<span class="author-affil"><span title="Szegedi Tudományegyetem">SZTE</span>/<span title="Szent-Györgyi Albert Orvostudományi Kar">SZAOK</span>/<span title="Belgyógyászati Klinika">BK</span>/I. sz. Belgyógyászati Klinika; <span title="Szegedi Tudományegyetem">SZTE</span>/<span title="Szent-Györgyi Albert Orvostudományi Kar">SZAOK</span>/<span title="Belgyógyászati Klinika">BK</span>/<span title="I. sz. Belgyógyászati Klinika">I.BelK</span>/MTA-SZTE Lendület Epitél Sejt Szignalizáció és Szekréció Kutatócsoport</span>
;
<span class="author-name" mtid="10027886"><a
href="/gui2/?type=authors&mode=browse&sel=10027886" target="_blank">Crul Tim
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<span class="author-affil"><span title="Szegedi Tudományegyetem">SZTE</span>/<span title="Szent-Györgyi Albert Orvostudományi Kar">SZAOK</span>/<span title="Belgyógyászati Klinika">BK</span>/<span title="I. sz. Belgyógyászati Klinika">I.BelK</span>/MTA-SZTE Lendület Epitél Sejt Szignalizáció és Szekréció Kutatócsoport</span>
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<span class="author-name" mtid="10050549"><a
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<span class="author-affil"><span title="Szegedi Tudományegyetem">SZTE</span>/<span title="Szent-Györgyi Albert Orvostudományi Kar">SZAOK</span>/<span title="Belgyógyászati Klinika">BK</span>/I. sz. Belgyógyászati Klinika; <span title="Szegedi Tudományegyetem">SZTE</span>/<span title="Szent-Györgyi Albert Orvostudományi Kar">SZAOK</span>/<span title="Belgyógyászati Klinika">BK</span>/<span title="I. sz. Belgyógyászati Klinika">I.BelK</span>/MTA-SZTE Lendület Epitél Sejt Szignalizáció és Szekréció Kutatócsoport</span>
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<span class="author-name" >Molnár Melinda
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<span class="author-name" mtid="10088774"><a
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<span class="author-affil"><span title="Szegedi Tudományegyetem">SZTE</span>/<span title="Szent-Györgyi Albert Orvostudományi Kar">SZAOK</span>/<span title="Belgyógyászati Klinika">BK</span>/<span title="I. sz. Belgyógyászati Klinika">I.BelK</span>/MTA-SZTE Lendület Epitél Sejt Szignalizáció és Szekréció Kutatócsoport</span>
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<span class="author-name" >Grassalkovich Anna
</span>
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<span class="author-name" mtid="10028385"><a
href="/gui2/?type=authors&mode=browse&sel=10028385" target="_blank">Szederkényi Edit
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<span class="author-affil"><span title="Szegedi Tudományegyetem">SZTE</span>/<span title="Szent-Györgyi Albert Orvostudományi Kar">SZAOK</span>/Sebészeti Klinika</span>
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<span class="author-name" mtid="10010110"><a
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<span class="author-affil"><span title="Szegedi Tudományegyetem">SZTE</span>/<span title="Szent-Györgyi Albert Orvostudományi Kar">SZAOK</span>/Sebészeti Klinika</span>
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<span class="author-name" mtid="10022556"><a
href="/gui2/?type=authors&mode=browse&sel=10022556" target="_blank">Venglovecz Viktória
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<span class="author-affil"><span title="Szegedi Tudományegyetem">SZTE</span>/<span title="Szent-Györgyi Albert Orvostudományi Kar">SZAOK</span>/Farmakológiai és Farmakoterápiai Intézet</span>
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<span class="author-name" mtid="10002629"><a
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<span class="author-affil"><span title="Pécsi Tudományegyetem">PTE</span>/<span title="Általános Orvostudományi Kar">ÁOK</span>/I.sz. Belgyógyászati Klinika; <span title="Szegedi Tudományegyetem">SZTE</span>/<span title="Szent-Györgyi Albert Orvostudományi Kar">SZAOK</span>/<span title="Belgyógyászati Klinika">BK</span>/I. sz. Belgyógyászati Klinika; <span title="Pécsi Tudományegyetem">PTE</span>/<span title="Általános Orvostudományi Kar">ÁOK</span>/Transzlációs Medicina Intézet; <span title="Semmelweis Egyetem">SE</span>/<span title="Központi Szervezeti Egységek (beleértve az Egyéb Szervezeti Egységeket)">KSZE</span>/Transzlációs Medicina Központ</span>
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<span class="author-name" mtid="10030084"><a
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<span class="author-affil"><span title="Szegedi Tudományegyetem">SZTE</span>/<span title="Szent-Györgyi Albert Orvostudományi Kar">SZAOK</span>/<span title="Belgyógyászati Klinika">BK</span>/I. sz. Belgyógyászati Klinika; <span title="Szegedi Tudományegyetem">SZTE</span>/<span title="Szent-Györgyi Albert Orvostudományi Kar">SZAOK</span>/<span title="Belgyógyászati Klinika">BK</span>/<span title="I. sz. Belgyógyászati Klinika">I.BelK</span>/MTA-SZTE Lendület Epitél Sejt Szignalizáció és Szekréció Kutatócsoport</span>
</div>
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<div class="title"><a href="/gui2/?mode=browse¶ms=publication;32624114" target="_blank">Bile acid- and ethanol-mediated activation of Orai1 damages pancreatic ductal secretion in acute pancreatitis</a></div> <div> <span class="journal-title">JOURNAL OF PHYSIOLOGY-LONDON</span>
<span class="journal-issn">(<a target="_blank" href="https://portal.issn.org/resource/ISSN/0022-3751">0022-3751</a> <a target="_blank" href="https://portal.issn.org/resource/ISSN/1469-7793">1469-7793</a>)</span>:
<span class="journal-volume">600</span> <span class="journal-issue">7</span>
<span class="page">
pp 1631-1650
</span> <span class="year">(2022)</span>
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Idézett közlemények száma: 17
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<div class="mtid"><span class="long-pub-mtid">Közlemény: 32624114</span>
| <span class="status-data status-VALIDATED"> Egyeztetett
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Forrás Idéző
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( Szakcikk
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| <span class="publication-sourceOfData">kézi felvitel</span>
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<div class="funder"> (GINOP-2.3.2-15-2016-00048—STAY ALIVE), (PD116553), EMBERI ERŐFORRÁS FEJLESZTÉSI OPERATÍV PROGRAM (EFOP)(EFOP-3.6.2-162017-00006) Támogató: NKFIH, (BO/00569/17) Támogató: MTA Bolyai pályázat, (LP2017–18/2017) Támogató: MTA, Smart rendszerek. Új Nemzeti Kiválóság Program(20391-3/2018/FEKUSTRAT) Támogató: EMMI, (TUDFO/47138-1/2019/ITM), Tématerületi Kiválósági Program 2021 - Transzlációs biomedicina(TKP2021-EGA-28) Támogató: NKFIH, Új Nemzeti Kiválóság Program(UNKP-21-4-SZTE-116) Támogató: Nemzeti Kutatás, Fejlesztés és Innovációs Iroda, (ÚNKP-21-3-SZTE-68), (Albert Szent-Györgyi Research Grant), Establishing the Hungarian Center of Excellence for Molecular Medicine in partnership with EMBL(739593) Támogató: Horizon 2020, (NTP-NFTÖ-B-0011), (NTP-NFTÖ-21-B-0079) </div>
<div class="lastModified">Utolsó módosítás: 2023.09.02. 15:49 Milánkovics Róbert (PTE ÁOK admin 4)
</div>
<pre class="comment" style="margin-top: 0; margin-bottom: 0;"><u>Megjegyzés</u>: * Megosztott szerzőség</pre>
</div></div>
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Department of Internal Medicine I, Ulm University Hospital, Ulm, Germany
Department of Urology, Ulm University, Ulm, Germany
Institute of Pathology, Ulm University, Ulm, Germany
Institute of Molecular Oncology and Functional Genomics, Center for Translational Cancer Research and Department of Medicine II, School of Medicine, Technical University of Munich, Munich, Germany
Chair of Proteomics and Bioanalytics, Technical University of Munich, Freising, Germany
Helmholtz Pioneer Campus, Helmholtz Zentrum München, Neuherberg, Germany
Paul Langerhans Institute Dresden (PLID) of the Helmholtz Zentrum München at the University Clinic Carl Gustav Carus of Technische Universität Dresden, Helmholtz Zentrum München, Neuherberg, Germany
Institute of Physiology, Faculty of Medicine, Technische Universität Dresden, Dresden, Germany
German Center for Diabetes Research (DZD), Neuherberg, Germany
First Department of Internal Medicine, University of Szeged, Szeged, Hungary
MTA-SZTE Momentum Epithelial Cell Signalling and Secretion Research Group, University of Szeged, Szeged, Hungary
Department of Cardiovascular & Metabolic Sciences, Lerner Research Institute, Cleveland, OH 44195, United States
Skeletal Biology Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, US Department of Health and Human Services, Bethesda, MD 20892, United States
Medical Clinic and Polyclinic II, Klinikum rechts der Isar, Technical University Munich, Munich, Germany
HCEMM-SZTE Molecular Gastroenterology Research Group, University of Szeged, Szeged, Hungary
Institute of Neuroanatomy & Developmental Biology (INDB), Eberhard Karls University Tübingen, Tübingen, Germany
Department of Internal Medicine VIII, University Hospital Tübingen, Tübingen, Germany
Bavarian Biomolecular Mass Spectrometry Center (BayBioMS), Technical University of Munich, Freising, Germany
Cited By :5
Export Date: 28 July 2021
Correspondence Address: Kleger, A.; Department of Internal Medicine I, Germany; email: alexander.kleger@uni-ulm.de
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Personalized in vitro models for dysplasia and carcinogenesis in the pancreas have been constrained by insufficient differentiation of human pluripotent stem cells (hPSCs) into the exocrine pancreatic lineage. Here, we differentiate hPSCs into pancreatic duct-like organoids (PDLOs) with morphological, transcriptional, proteomic, and functional characteristics of human pancreatic ducts, further maturing upon transplantation into mice. PDLOs are generated from hPSCs inducibly expressing oncogenic GNAS, KRAS, or KRAS with genetic covariance of lost CDKN2A and from induced hPSCs derived from a McCune-Albright patient. Each oncogene causes a specific growth, structural, and molecular phenotype in vitro. While transplanted PDLOs with oncogenic KRAS alone form heterogenous dysplastic lesions or cancer, KRAS with CDKN2A loss develop dedifferentiated pancreatic ductal adenocarcinomas. In contrast, transplanted PDLOs with mutant GNAS lead to intraductal papillary mucinous neoplasia-like structures. Conclusively, PDLOs enable in vitro and in vivo studies of pancreatic plasticity, dysplasia, and cancer formation from a genetically defined background.
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<div class="JournalArticle Publication short-list"> <div class="authors"> <span class="author-name" > Breunig, Markus </span> <span class="author-type"> </span> ; <span class="author-name" > Merkle, Jessica </span> <span class="author-type"> </span> ; <span class="author-name" > Wagner, Martin </span> <span class="author-type"> </span> ; <span class="author-name" > Melzer, Michael K </span> <span class="author-type"> </span> ; <span class="author-name" > Barth, Thomas F E </span> <span class="author-type"> </span> ; <span class="author-name" > Engleitner, Thomas </span> <span class="author-type"> </span> ; <span class="author-name" > Krumm, Johannes </span> <span class="author-type"> </span> ; <span class="author-name" > Wiedenmann, Sandra </span> <span class="author-type"> </span> ; <span class="author-name" > Cohrs, Christian M </span> <span class="author-type"> </span> ; <span class="author-name" > Perkhofer, Lukas </span> <span class="author-type"> </span> et al. </div ><div class="title"><a href="/gui2/?mode=browse¶ms=publication;31999456" mtid="31999456" target="_blank">Modeling plasticity and dysplasia of pancreatic ductal organoids derived from human pluripotent stem cells</a></div> <div class="pub-info"> <span class="journal-title">CELL STEM CELL</span> <span class="journal-volume">28</span> : <span class="journal-issue">6</span> <span class="page"> pp. 1105-1124. , 19 p. </span> <span class="year">(2021)</span> </div> <div class="pub-end"><div class="identifier-list"> <span class="identifiers"> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="10.1016/j.stem.2021.03.005" target="_blank" href="https://doi.org/10.1016/j.stem.2021.03.005"> DOI </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="000658938000014" target="_blank" href="https://www.webofscience.com/wos/woscc/full-record/000658938000014"> WoS </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="85105105008" target="_blank" href="http://www.scopus.com/record/display.url?origin=inward&eid=2-s2.0-85105105008"> Scopus </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="33915078" target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=33915078&dopt=Abstract"> PubMed </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:black" title="15805293021194990015" target="_blank" href="http://scholar.Google.com/scholar?hl=en&lr=&cluster=15805293021194990015"> Google scholar </a> </span> <span class="id identifier oa_GREEN" title=" Green "> <a style="color:blue" title="27497" target="_blank" href="http://publicatio.bibl.u-szeged.hu/27497"> SZTE Publicatio </a> </span> </span> </div> <div class="short-pub-prop-list"> <span class="short-pub-mtid"> Közlemény:31999456 </span> <span class="status-holder"><span class="status-data status-VALIDATED"> Egyeztetett </span></span> <span class="pub-core">Forrás Idéző </span> <span class="pub-type">Folyóiratcikk (Sokszerzős vagy csoportos szerzőségű szakcikk ) </span> <!-- && !record.category.scientific --> <span class="pub-category">Tudományos</span> <div class="publication-citation" style="margin-left: 0.5cm;"> <span title="Nyilvános idézőközlemények összesen, említések nélkül" class="citingPub-count">Nyilvános idéző összesen: 56</span> | Független: 37 | Függő: 19 | Nem jelölt: 0 | WoS jelölt: 55 | Scopus jelölt: 51 | WoS/Scopus jelölt: 55 | DOI jelölt: 54 </div> </div> </div> </div><div class="JournalArticle Publication long-list">
<div class="authors">
<img title="Forrásközlemény" style="float: left" src="/frontend/resources/grid/publication-core-icon.png">
<img title="Idézőközlemény" style="float: left" src="/frontend/resources/grid/publication-citation-icon.png">
<div class="autype autype0"> <span class="author-name" >Breunig Markus
</span>
;
<span class="author-name" mtid="10059215"><a
href="/gui2/?type=authors&mode=browse&sel=10059215" target="_blank">Madácsy Tamara
(<span class="authorship-author-name">Madácsy Tamara</span>
<span class="authorAux-mtmt"> sejtélettan</span>)
</a>
</span>
<span class="author-affil"><span title="Szegedi Tudományegyetem">SZTE</span>/<span title="Általános Orvostudományi Kar">ÁOK</span>/<span title="Belgyógyászati Klinika">BK</span>/I. sz. Belgyógyászati Klinika; <span title="Szegedi Tudományegyetem">SZTE</span>/<span title="Általános Orvostudományi Kar">ÁOK</span>/<span title="Belgyógyászati Klinika">BK</span>/<span title="I. sz. Belgyógyászati Klinika">I.BelK</span>/MTA-SZTE Lendület Epitél Sejt Szignalizáció és Szekréció Kutatócsoport</span>
;
<span class="author-name" mtid="10061075"><a
href="/gui2/?type=authors&mode=browse&sel=10061075" target="_blank">Varga Árpád
(<span class="authorship-author-name">Varga Árpád</span>
<span class="authorAux-mtmt"> Sejt- és molekuláris biológia</span>)
</a>
</span>
<span class="author-affil"><span title="Szegedi Tudományegyetem">SZTE</span>/<span title="Általános Orvostudományi Kar">ÁOK</span>/<span title="Belgyógyászati Klinika">BK</span>/I. sz. Belgyógyászati Klinika; <span title="Szegedi Tudományegyetem">SZTE</span>/<span title="Általános Orvostudományi Kar">ÁOK</span>/<span title="Belgyógyászati Klinika">BK</span>/<span title="I. sz. Belgyógyászati Klinika">I.BelK</span>/MTA-SZTE Lendület Epitél Sejt Szignalizáció és Szekréció Kutatócsoport</span>
;
<span class="author-name" mtid="10030084"><a
href="/gui2/?type=authors&mode=browse&sel=10030084" target="_blank">Maléth József
(<span class="authorship-author-name">Maléth József</span>
<span class="authorAux-mtmt"> Gasztroenterológia</span>)
</a>
</span>
<span class="author-affil"><span title="Szegedi Tudományegyetem">SZTE</span>/<span title="Általános Orvostudományi Kar">ÁOK</span>/<span title="Belgyógyászati Klinika">BK</span>/I. sz. Belgyógyászati Klinika; <span title="Szegedi Tudományegyetem">SZTE</span>/<span title="Általános Orvostudományi Kar">ÁOK</span>/<span title="Belgyógyászati Klinika">BK</span>/<span title="I. sz. Belgyógyászati Klinika">I.BelK</span>/MTA-SZTE Lendület Gasztroenterológiai Multidiszciplináris Kutatócsoport; <span title="Szegedi Tudományegyetem">SZTE</span>/<span title="Általános Orvostudományi Kar">ÁOK</span>/<span title="Belgyógyászati Klinika">BK</span>/<span title="I. sz. Belgyógyászati Klinika">I.BelK</span>/MTA-SZTE Lendület Epitél Sejt Szignalizáció és Szekréció Kutatócsoport</span>
;
et al. (37)
</div>
<div><a target="_blank" href="/api/publication/31999456?labelLang=hun">Összes szerző</a></div>
</div>
<div class="title"><a href="/gui2/?mode=browse¶ms=publication;31999456" target="_blank">Modeling plasticity and dysplasia of pancreatic ductal organoids derived from human pluripotent stem cells</a></div> <div> <span class="journal-title">CELL STEM CELL</span>
<span class="journal-issn">(<a target="_blank" href="https://portal.issn.org/resource/ISSN/1934-5909">1934-5909</a> <a target="_blank" href="https://portal.issn.org/resource/ISSN/1875-9777">1875-9777</a>)</span>:
<span class="journal-volume">28</span> <span class="journal-issue">6</span>
<span class="page">
pp 1105-1124
</span> <span class="year">(2021)</span>
</div>
<div class="pub-footer">
<span class="language" xmlns="http://www.w3.org/1999/html">Nyelv:
Angol
| </span>
<span class="identifiers">
<span class="id identifier oa_none" title="none">
<a style="color:blue" title="10.1016/j.stem.2021.03.005" target="_blank" href="https://doi.org/10.1016/j.stem.2021.03.005">
DOI
</a>
</span>
<span class="id identifier oa_none" title="none">
<a style="color:blue" title="000658938000014" target="_blank" href="https://www.webofscience.com/wos/woscc/full-record/000658938000014">
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<a style="color:blue" title="85105105008" target="_blank" href="http://www.scopus.com/record/display.url?origin=inward&eid=2-s2.0-85105105008">
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<pre class="comment" style="margin-top: 0; margin-bottom: 0;"><u>Megjegyzés</u>: Department of Internal Medicine I, Ulm University Hospital, Ulm, Germany
Department of Urology, Ulm University, Ulm, Germany
Institute of Pathology, Ulm University, Ulm, Germany
Institute of Molecular Oncology and Functional Genomics, Center for Translational Cancer Research and Department of Medicine II, School of Medicine...</pre>
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Funding text: The research was supported by funding from the Hungarian National Research, Development and Innovation Office (GINOP-2.3.2-15-2016-00048 to JM), the Ministry of Human Capacities (EFOP 3.6.2-16-2017-00006 to JM), the Hungarian Academy of Sciences (LP2017-18/2017 to JM), by the National Excellence Program (20391-3/2018/FEKUSTRAT, TUDFO/47138-1/2019/ITM and TKP2020) to JM. This work was supported by Albert Szent-Gyorgyi Research Grant (to JM) by the Faculty of Medicine. The project has received funding from the EU's Horizon 2020 research and innovation program under grant agreement No. 739593.
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<div class="JournalArticle Publication short-list"> <div class="authors"> <span class="author-name" mtid="10027886"> <a href="/gui2/?type=authors&mode=browse&sel=10027886" target="_blank">Crul, Tim ✉</a> </span> <span class="author-type"> </span> ; <span class="author-name" mtid="10030084"> <a href="/gui2/?type=authors&mode=browse&sel=10030084" target="_blank">Maléth, József ✉</a> </span> <span class="author-type"> </span> </div ><div class="title"><a href="/gui2/?mode=browse¶ms=publication;31993815" mtid="31993815" target="_blank">Endoplasmic Reticulum‐Plasma Membrane Contact Sites as an Organizing Principle for Compartmentalized Calcium and cAMP Signaling</a></div> <div class="pub-info"> <span class="journal-title">INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES</span> <span class="journal-volume">22</span> : <span class="journal-issue">9</span> <span class="page"> Paper: 4703 , 26 p. </span> <span class="year">(2021)</span> </div> <div class="pub-end"><div class="identifier-list"> <span class="identifiers"> <span class="id identifier oa_GOLD" title=" Gold "> <a style="color:blue" title="10.3390/ijms22094703" target="_blank" href="https://doi.org/10.3390/ijms22094703"> DOI </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="000650393800001" target="_blank" href="https://www.webofscience.com/wos/woscc/full-record/000650393800001"> WoS </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="85105431910" target="_blank" href="http://www.scopus.com/record/display.url?origin=inward&eid=2-s2.0-85105431910"> Scopus </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="33946838" target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=33946838&dopt=Abstract"> PubMed </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:black" title="https://www.mdpi.com/1422-0067/22/9/4703" target="_blank" href="https://www.mdpi.com/1422-0067/22/9/4703"> Egyéb URL </a> </span> <span class="id identifier oa_GREEN" title=" Green "> <a style="color:blue" title="21958" target="_blank" href="http://publicatio.bibl.u-szeged.hu/21958"> SZTE Publicatio </a> </span> </span> </div> <div class="short-pub-prop-list"> <span class="short-pub-mtid"> Közlemény:31993815 </span> <span class="status-holder"><span class="status-data status-VALIDATED"> Egyeztetett </span></span> <span class="pub-core">Forrás Idéző </span> <span class="pub-type">Folyóiratcikk (Összefoglaló cikk ) </span> <!-- && !record.category.scientific --> <span class="pub-category">Tudományos</span> <div class="publication-citation" style="margin-left: 0.5cm;"> <span title="Nyilvános idézőközlemények összesen, említések nélkül" class="citingPub-count">Nyilvános idéző összesen: 9</span> | Független: 9 | Függő: 0 | Nem jelölt: 0 | WoS jelölt: 7 | Scopus jelölt: 9 | WoS/Scopus jelölt: 9 | DOI jelölt: 9 </div> </div> </div> </div><div class="JournalArticle Publication long-list">
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<div class="title"><a href="/gui2/?mode=browse¶ms=publication;31993815" target="_blank">Endoplasmic Reticulum‐Plasma Membrane Contact Sites as an Organizing Principle for Compartmentalized Calcium and cAMP Signaling</a></div> <div> <span class="journal-title">INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES</span>
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<div class="funder"> GINOP - STAY ALIVE(GINOP-2.3.2-15-2016-00048) Támogató: Nemzeti Kutatási, Fejlesztési és Innovációs Hivatal, EMBERI ERŐFORRÁS FEJLESZTÉSI OPERATÍV PROGRAM (EFOP)(EFOP-3.6.2-162017-00006) Támogató: NKFIH, (LP2017–18/2017) Támogató: MTA, Smart rendszerek. Új Nemzeti Kiválóság Program(20391-3/2018/FEKUSTRAT) Támogató: EMMI, Felsőoktatási Intézményi Kiválósági Program (2019)(TUDFO/47138/2019-ITM) Támogató: ITM, Establishing the Hungarian Center of Excellence for Molecular Medicine in partnership with EMBL(739593) Támogató: Horizon 2020 </div>
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<pre class="comment" style="margin-top: 0; margin-bottom: 0;"><u>Megjegyzés</u>: Funding Agency and Grant Number: Hungarian National Research, Development and Innovation Office [GINOP-2.3.2-15-2016-00048]; Ministry of Human Capacities [EFOP 3.6.2-16-2017-00006]; Hungarian Academy of SciencesHungarian Academy of Sciences [LP2017-18/2017]; National Excellence Program [20391-3/2018/FEKUSTRAT, TUDFO/47138-1/2019/ITM, TKP2020]; Albert Szent-Gyorgyi Research Grant by the Faculty ...</pre>
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<div class="JournalArticle Publication short-list"> <div class="authors"> <span class="author-name" mtid="10061030"> <a href="/gui2/?type=authors&mode=browse&sel=10061030" target="_blank">Kata Judit, Szántó</a> </span> <span class="author-type"> </span> ; <span class="author-name" mtid="10059215"> <a href="/gui2/?type=authors&mode=browse&sel=10059215" target="_blank">Tamara, Madácsy<sup>*</sup></a> </span> <span class="author-type"> </span> ; <span class="author-name" mtid="10053249"> <a href="/gui2/?type=authors&mode=browse&sel=10053249" target="_blank">Diána, Kata</a> </span> <span class="author-type"> </span> ; <span class="author-name" mtid="10036214"> <a href="/gui2/?type=authors&mode=browse&sel=10036214" target="_blank">Tamás, Ferenci</a> </span> <span class="author-type"> </span> ; <span class="author-name" mtid="10050453"> <a href="/gui2/?type=authors&mode=browse&sel=10050453" target="_blank">Mariann, Rutka</a> </span> <span class="author-type"> </span> ; <span class="author-name" mtid="10040713"> <a href="/gui2/?type=authors&mode=browse&sel=10040713" target="_blank">Anita, Bálint</a> </span> <span class="author-type"> </span> ; <span class="author-name" mtid="10050454"> <a href="/gui2/?type=authors&mode=browse&sel=10050454" target="_blank">Renáta, Bor</a> </span> <span class="author-type"> </span> ; <span class="author-name" mtid="10059872"> <a href="/gui2/?type=authors&mode=browse&sel=10059872" target="_blank">Anna, Fábián</a> </span> <span class="author-type"> </span> ; <span class="author-name" mtid="10059868"> <a href="/gui2/?type=authors&mode=browse&sel=10059868" target="_blank">Ágnes, Milassin</a> </span> <span class="author-type"> </span> ; <span class="author-name" mtid="10072590"> <a href="/gui2/?type=authors&mode=browse&sel=10072590" target="_blank">Boldizsár, Jójárt</a> </span> <span class="author-type"> </span> et al. </div ><div class="title"><a href="/gui2/?mode=browse¶ms=publication;31902690" mtid="31902690" target="_blank">Advances in the optimization of therapeutic drug monitoring using serum, tissue and faecal anti-tumour necrosis factor concentration in patients with inflammatory bowel disease treated with TNF-α antagonists</a></div> <div class="pub-info"> <span class="journal-title">EXPERT OPINION ON BIOLOGICAL THERAPY</span> <span class="journal-volume">21</span> : <span class="journal-issue">4</span> <span class="page"> pp. 539-548. , 10 p. </span> <span class="year">(2021)</span> </div> <div class="pub-end"><div class="identifier-list"> <span class="identifiers"> <span class="id identifier oa_PAY" title=" Fizetős "> <a style="color:blue" title="10.1080/14712598.2021.1890712" target="_blank" href="https://doi.org/10.1080/14712598.2021.1890712"> DOI </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="000625997800001" target="_blank" href="https://www.webofscience.com/wos/woscc/full-record/000625997800001"> WoS </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="85104649143" target="_blank" href="http://www.scopus.com/record/display.url?origin=inward&eid=2-s2.0-85104649143"> Scopus </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="33583295" target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=33583295&dopt=Abstract"> PubMed </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="https://www.tandfonline.com/doi/full/10.1080/14712598.2021.1890712" target="_blank" href="https://www.tandfonline.com/doi/full/10.1080/14712598.2021.1890712"> Egyéb URL </a> </span> <span class="id identifier oa_RESTRICTED" title=" Korlátozott "> <a style="color:blue" title="21270" target="_blank" href="http://publicatio.bibl.u-szeged.hu/21270"> SZTE Publicatio </a> </span> </span> </div> <div class="short-pub-prop-list"> <span class="short-pub-mtid"> Közlemény:31902690 </span> <span class="status-holder"><span class="status-data status-VALIDATED"> Egyeztetett </span></span> <span class="pub-core">Forrás Idéző </span> <span class="pub-type">Folyóiratcikk (Szakcikk ) </span> <!-- && !record.category.scientific --> <span class="pub-category">Tudományos</span> <div class="publication-citation" style="margin-left: 0.5cm;"> <span title="Nyilvános idézőközlemények összesen, említések nélkül" class="citingPub-count">Nyilvános idéző összesen: 6</span> | Független: 6 | Függő: 0 | Nem jelölt: 0 | WoS jelölt: 5 | Scopus jelölt: 4 | WoS/Scopus jelölt: 5 | DOI jelölt: 6 </div> </div> </div> </div><div class="JournalArticle Publication long-list"> <div class="authors"> <img title="Forrásközlemény" style="float: left" src="/frontend/resources/grid/publication-core-icon.png"> <img title="Idézőközlemény" style="float: left" src="/frontend/resources/grid/publication-citation-icon.png"> <div class="autype autype0"> <span class="author-name" mtid="10061030"><a href="/gui2/?type=authors&mode=browse&sel=10061030" target="_blank">Kata Judit Szántó (<span class="authorship-author-name">Szántó Kata Judit</span> <span class="authorAux-mtmt"> bélbetegségek</span>) </a> </span> <span class="author-affil"><span title="Szegedi Tudományegyetem">SZTE</span>/<span title="Általános Orvostudományi Kar">ÁOK</span>/<span title="Belgyógyászati Klinika">BK</span>/I. sz. Belgyógyászati Klinika</span> ; <span class="author-name" mtid="10059215"><a href="/gui2/?type=authors&mode=browse&sel=10059215" target="_blank">Tamara Madácsy<sup>*</sup> (<span class="authorship-author-name">Madácsy Tamara</span> <span class="authorAux-mtmt"> sejtélettan</span>) </a> </span> <span class="author-affil"><span title="Szegedi Tudományegyetem">SZTE</span>/<span title="Általános Orvostudományi Kar">ÁOK</span>/<span title="Belgyógyászati Klinika">BK</span>/I. sz. Belgyógyászati Klinika</span> ; <span class="author-name" mtid="10053249"><a href="/gui2/?type=authors&mode=browse&sel=10053249" target="_blank">Diána Kata (<span class="authorship-author-name">Kata Diána</span> <span class="authorAux-mtmt"> Idegtudomány</span>) </a> </span> <span class="author-affil"><span title="Szegedi Tudományegyetem">SZTE</span>/<span title="Szent-Györgyi Albert Orvostudományi Kar">SZAOK</span>/Laboratóriumi Medicina Intézet</span> ; <span class="author-name" mtid="10036214"><a href="/gui2/?type=authors&mode=browse&sel=10036214" target="_blank">Tamás Ferenci (<span class="authorship-author-name">Ferenci Tamás</span> <span class="authorAux-mtmt"> Biostatisztika</span>) </a> </span> <span class="author-affil"><span title="Budapesti Corvinus Egyetem">BCE</span>/<span title="Matematikai és Statisztikai Modellezés Intézet">MSMI</span>/Statisztika Tanszék; <span title="Óbudai Egyetem">ÓE</span>/<span title="Neumann János Informatikai Kar">NIK</span>/Biomatika és Alkalmazott Mesterséges Intelligencia Intézet</span> ; <span class="author-name" mtid="10050453"><a href="/gui2/?type=authors&mode=browse&sel=10050453" target="_blank">Mariann Rutka (<span class="authorship-author-name">Rutka Mariann</span> <span class="authorAux-mtmt"> Belgyógyászat- Gasztroenterológia</span>) </a> </span> <span class="author-affil"><span title="Szegedi Tudományegyetem">SZTE</span>/<span title="Általános Orvostudományi Kar">ÁOK</span>/<span title="Belgyógyászati Klinika">BK</span>/I. sz. Belgyógyászati Klinika</span> ; <span class="author-name" mtid="10040713"><a href="/gui2/?type=authors&mode=browse&sel=10040713" target="_blank">Anita Bálint (<span class="authorship-author-name">Bálint Anita</span> <span class="authorAux-mtmt"> Gastroenterológia</span>) </a> </span> <span class="author-affil"><span title="Szegedi Tudományegyetem">SZTE</span>/<span title="Általános Orvostudományi Kar">ÁOK</span>/<span title="Belgyógyászati Klinika">BK</span>/I. sz. Belgyógyászati Klinika</span> ; <span class="author-name" mtid="10050454"><a href="/gui2/?type=authors&mode=browse&sel=10050454" target="_blank">Renáta Bor (<span class="authorship-author-name">Bor Renáta</span> <span class="authorAux-mtmt"> gasztroenterológia</span>) </a> </span> <span class="author-affil"><span title="Szegedi Tudományegyetem">SZTE</span>/<span title="Általános Orvostudományi Kar">ÁOK</span>/<span title="Belgyógyászati Klinika">BK</span>/I. sz. Belgyógyászati Klinika</span> ; <span class="author-name" mtid="10059872"><a href="/gui2/?type=authors&mode=browse&sel=10059872" target="_blank">Anna Fábián (<span class="authorship-author-name">Fábián Anna</span> <span class="authorAux-mtmt"> belgyógyászat</span>) </a> </span> <span class="author-affil"><span title="Szegedi Tudományegyetem">SZTE</span>/<span title="Általános Orvostudományi Kar">ÁOK</span>/<span title="Belgyógyászati Klinika">BK</span>/I. sz. Belgyógyászati Klinika</span> ; <span class="author-name" mtid="10059868"><a href="/gui2/?type=authors&mode=browse&sel=10059868" target="_blank">Ágnes Milassin (<span class="authorship-author-name">Milassin Ágnes</span> <span class="authorAux-mtmt"> belgyógyászat</span>) </a> </span> <span class="author-affil"><span title="Szegedi Tudományegyetem">SZTE</span>/<span title="Általános Orvostudományi Kar">ÁOK</span>/<span title="Belgyógyászati Klinika">BK</span>/I. sz. Belgyógyászati Klinika</span> ; <span class="author-name" mtid="10072590"><a href="/gui2/?type=authors&mode=browse&sel=10072590" target="_blank">Boldizsár Jójárt (<span class="authorship-author-name">Jójárt Boldizsár</span> <span class="authorAux-mtmt"> immunológia, molekuláris biológia, gasztroenter...</span>) </a> </span> <span class="author-affil"><span title="Szegedi Tudományegyetem">SZTE</span>/<span title="Általános Orvostudományi Kar">ÁOK</span>/<span title="Belgyógyászati Klinika">BK</span>/I. sz. Belgyógyászati Klinika</span> ; <span class="author-name" mtid="10029706"><a href="/gui2/?type=authors&mode=browse&sel=10029706" target="_blank">Zoltán Szepes (<span class="authorship-author-name">Szepes Zoltán</span> <span class="authorAux-mtmt"> belgyógyászat, gasztroenterológia</span>) </a> </span> <span class="author-affil"><span title="Szegedi Tudományegyetem">SZTE</span>/<span title="Általános Orvostudományi Kar">ÁOK</span>/<span title="Belgyógyászati Klinika">BK</span>/I. sz. Belgyógyászati Klinika</span> ; <span class="author-name" mtid="10009508"><a href="/gui2/?type=authors&mode=browse&sel=10009508" target="_blank">Ferenc Nagy (<span class="authorship-author-name">Nagy Ferenc</span> <span class="authorAux-mtmt"> Gastroenterológia</span>) </a> </span> <span class="author-affil"><span title="Szegedi Tudományegyetem">SZTE</span>/<span title="Általános Orvostudományi Kar">ÁOK</span>/<span title="Belgyógyászati Klinika">BK</span>/I. sz. Belgyógyászati Klinika</span> ; <span class="author-name" mtid="10027340"><a href="/gui2/?type=authors&mode=browse&sel=10027340" target="_blank">Tamás Molnár (<span class="authorship-author-name">Molnár Tamás</span> <span class="authorAux-mtmt"> belgyógyászat-gasztroenterológia</span>) </a> </span> <span class="author-affil"><span title="Szegedi Tudományegyetem">SZTE</span>/<span title="Általános Orvostudományi Kar">ÁOK</span>/<span title="Belgyógyászati Klinika">BK</span>/I. sz. Belgyógyászati Klinika</span> ; <span class="author-name" mtid="10029238"><a href="/gui2/?type=authors&mode=browse&sel=10029238" target="_blank">Imre Földesi (<span class="authorship-author-name">Földesi Imre</span> <span class="authorAux-mtmt"> belgyógyászat, endokrinológia</span>) </a> </span> <span class="author-affil"><span title="Szegedi Tudományegyetem">SZTE</span>/<span title="Szent-Györgyi Albert Orvostudományi Kar">SZAOK</span>/Laboratóriumi Medicina Intézet</span> ; <span class="author-name" mtid="10030084"><a href="/gui2/?type=authors&mode=browse&sel=10030084" target="_blank">József Maléth<sup>**</sup> ✉ (<span class="authorship-author-name">Maléth József</span> <span class="authorAux-mtmt"> Gasztroenterológia</span>) </a> </span> <span class="author-affil"><span title="Szegedi Tudományegyetem">SZTE</span>/<span title="Általános Orvostudományi Kar">ÁOK</span>/<span title="Belgyógyászati Klinika">BK</span>/I. sz. 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Új Nemzeti Kiválóság Program(20391-3/2018/FEKUSTRAT) Támogató: EMMI, (UNKP-18-3-I-SZTE-66), Az orvos-, egészségtudományi- és gyógyszerészképzés tudományos műhelyeinek fejlesztése(EFOP-3.6.3-VEKOP-16-2017-00009) Támogató: EFOP-VEKOP, Establishing the Hungarian Center of Excellence for Molecular Medicine in partnership with EMBL(739593) Támogató: Horizon 2020 </div> <div class="lastModified">Utolsó módosítás: 2023.12.19. 22:24 Bernátskyné Babus Csilla (SZTE admin4) </div> </div></div>
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TRPM2-mediated extracellular Ca2+ entry promotes acinar cell necrosis in biliary acute pancreatitis
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Acute biliary pancreatitis is a significant clinical challenge as currently no specific pharmaceutical treatment exists. Intracellular Ca2+ overload, increased reactive oxygen species (ROS) production, mitochondrial damage and intra-acinar digestive enzyme activation caused by bile acids are hallmarks of acute biliary pancreatitis. Transient Receptor Potential Melastatin 2 (TRPM2) is a non-selective cation channel that has recently emerged as an important contributor to oxidative-stress-induced cellular Ca2+ overload across different diseases. We demonstrated that TRPM2 is expressed in the plasma membrane of mouse pancreatic acinar and ductal cells, which can be activated by increased oxidative stress induced by H2 O2 treatment and contributed to bile acid-induced extracellular Ca2+ influx in acinar cells, which promoted acinar cell necrosis in vitro and in vivo. These results suggest that the inhibition of TRPM2 may be a potential treatment option for biliary pancreatitis.Acute biliary pancreatitis poses a significant clinical challenge as currently no specific pharmaceutical treatment exists. Disturbed intracellular Ca2+ signalling caused by bile acids is a hallmark of the disease, which induces increased reactive oxygen species (ROS) production, mitochondrial damage, intra-acinar digestive enzyme activation and cell death. Because of this mechanism of action, prevention of toxic cellular Ca2+ overload is a promising therapeutic target. Transient Receptor Potential Melastatin 2 (TRPM2) is a non-selective cation channel that has recently emerged as an important contributor to oxidative-stress-induced cellular Ca2+ overload across different diseases. However, the expression and possible functions of TRPM2 in the exocrine pancreas remain unknown. Here we found that TRPM2 is expressed in the plasma membrane of mouse pancreatic acinar and ductal cells, which can be activated by increased oxidative stress induced by H2 O2 treatment. TRPM2 activity was found to contribute to bile acid-induced extracellular Ca2+ influx in acinar cells, but did not have the same effect in ductal cells. The generation of intracellular ROS in response to bile acids was remarkably higher in pancreatic acinar cells compared to isolated ducts, which can explain the difference between acinar and ductal cells. This activity promoted acinar cell necrosis in vitro independently from mitochondrial damage or mitochondrial fragmentation. In addition, bile-acid-induced experimental pancreatitis was less severe in TRPM2 knockout mice, whereas the lack of TRPM2 had no protective effect in cerulein induced acute pancreatitis. Our results suggest that the inhibition of TRPM2 may be a potential treatment option for biliary pancreatitis. This article is protected by copyright. All rights reserved.
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<div class="JournalArticle Publication short-list"> <div class="authors"> <span class="author-name" mtid="10054985"> <a href="/gui2/?type=authors&mode=browse&sel=10054985" target="_blank">Fanczal, Júlia</a> </span> <span class="author-type"> </span> ; <span class="author-name" mtid="10030075"> <a href="/gui2/?type=authors&mode=browse&sel=10030075" target="_blank">Pallagi, Petra<sup>*</sup></a> </span> <span class="author-type"> </span> ; <span class="author-name" mtid="10080809"> <a href="/gui2/?type=authors&mode=browse&sel=10080809" target="_blank">Görög, Marietta</a> </span> <span class="author-type"> </span> ; <span class="author-name" mtid="10058722"> <a href="/gui2/?type=authors&mode=browse&sel=10058722" target="_blank">Diszházi, Gyula</a> </span> <span class="author-type"> </span> ; <span class="author-name" mtid="10034375"> <a href="/gui2/?type=authors&mode=browse&sel=10034375" target="_blank">Almássy, János</a> </span> <span class="author-type"> </span> ; <span class="author-name" mtid="10059215"> <a href="/gui2/?type=authors&mode=browse&sel=10059215" target="_blank">Madácsy, Tamara</a> </span> <span class="author-type"> </span> ; <span class="author-name" mtid="10061075"> <a href="/gui2/?type=authors&mode=browse&sel=10061075" target="_blank">Varga, Árpád</a> </span> <span class="author-type"> </span> ; <span class="author-name" > Csernay-Biró, Péter </span> <span class="author-type"> </span> ; <span class="author-name" mtid="10059078"> <a href="/gui2/?type=authors&mode=browse&sel=10059078" target="_blank">Katona, Xénia</a> </span> <span class="author-type"> </span> ; <span class="author-name" mtid="10054987"> <a href="/gui2/?type=authors&mode=browse&sel=10054987" target="_blank">Tóth, Emese</a> </span> <span class="author-type"> </span> et al. </div ><div class="title"><a href="/gui2/?mode=browse¶ms=publication;31097108" mtid="31097108" target="_blank">TRPM2-mediated extracellular Ca2+ entry promotes acinar cell necrosis in biliary acute pancreatitis</a></div> <div class="pub-info"> <span class="journal-title">JOURNAL OF PHYSIOLOGY-LONDON</span> <span class="journal-volume">598</span> : <span class="journal-issue">6</span> <span class="page"> pp. 1253-1270. , 18 p. </span> <span class="year">(2020)</span> </div> <div class="pub-end"><div class="identifier-list"> <span class="identifiers"> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="10.1113/JP279047" target="_blank" href="https://doi.org/10.1113/JP279047"> DOI </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="000511350000001" target="_blank" href="https://www.webofscience.com/wos/woscc/full-record/000511350000001"> WoS </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="85079060274" target="_blank" href="http://www.scopus.com/record/display.url?origin=inward&eid=2-s2.0-85079060274"> Scopus </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="31917868" target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=31917868&dopt=Abstract"> PubMed </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:black" title="12477552805439928534" target="_blank" href="http://scholar.Google.com/scholar?hl=en&lr=&cluster=12477552805439928534"> Google scholar </a> </span> <span class="id identifier oa_GREEN" title=" Green "> <a style="color:blue" title="18333" target="_blank" href="http://publicatio.bibl.u-szeged.hu/18333"> SZTE Publicatio </a> </span> </span> </div> <div class="short-pub-prop-list"> <span class="short-pub-mtid"> Közlemény:31097108 </span> <span class="status-holder"><span class="status-data status-VALIDATED"> Egyeztetett </span></span> <span class="pub-core">Forrás Idéző </span> <span class="pub-type">Folyóiratcikk (Szakcikk ) </span> <!-- && !record.category.scientific --> <span class="pub-category">Tudományos</span> <div class="publication-citation" style="margin-left: 0.5cm;"> <span title="Nyilvános idézőközlemények összesen, említések nélkül" class="citingPub-count">Nyilvános idéző összesen: 22</span> | Független: 17 | Függő: 5 | Nem jelölt: 0 | WoS jelölt: 16 | Scopus jelölt: 18 | WoS/Scopus jelölt: 18 | DOI jelölt: 21 </div> </div> </div> </div><div class="JournalArticle Publication long-list">
<div class="authors">
<img title="Forrásközlemény" style="float: left" src="/frontend/resources/grid/publication-core-icon.png">
<img title="Idézőközlemény" style="float: left" src="/frontend/resources/grid/publication-citation-icon.png">
<div class="autype autype0"> <span class="author-name" mtid="10054985"><a
href="/gui2/?type=authors&mode=browse&sel=10054985" target="_blank">Fanczal Júlia
(<span class="authorship-author-name">Fanczal Júlia</span>
<span class="authorAux-mtmt"> pancreatitis (alapkutatás)</span>)
</a>
</span>
<span class="author-affil"><span title="Szegedi Tudományegyetem">SZTE</span>/<span title="Általános Orvostudományi Kar">ÁOK</span>/<span title="Belgyógyászati Klinika">BK</span>/<span title="I. sz. Belgyógyászati Klinika">I.BelK</span>/MTA-SZTE Lendület Epitél Sejt Szignalizáció és Szekréció Kutatócsoport</span>
;
<span class="author-name" mtid="10030075"><a
href="/gui2/?type=authors&mode=browse&sel=10030075" target="_blank">Pallagi Petra<sup>*</sup>
(<span class="authorship-author-name">Pallagi Petra</span>
<span class="authorAux-mtmt"> Gasztroenterológia</span>)
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<div class="title"><a href="/gui2/?mode=browse¶ms=publication;31097108" target="_blank">TRPM2-mediated extracellular Ca2+ entry promotes acinar cell necrosis in biliary acute pancreatitis</a></div> <div> <span class="journal-title">JOURNAL OF PHYSIOLOGY-LONDON</span>
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| Függő: 5
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<div class="mtid"><span class="long-pub-mtid">Közlemény: 31097108</span>
| <span class="status-data status-VALIDATED"> Egyeztetett
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Forrás Idéző
| <span class="type-subtype">Folyóiratcikk
( Szakcikk
)
</span>
| <span class="pub-category">Tudományos</span>
| <span class="publication-sourceOfData">PubMed XML</span>
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<div class="funder"> EMBERI ERŐFORRÁS FEJLESZTÉSI OPERATÍV PROGRAM (EFOP)(EFOP-3.6.2-162017-00006) Támogató: NKFIH, Az orvos-, egészségtudományi- és gyógyszerészképzés tudományos műhelyeinek fejlesztése(EFOP-3.6.3-VEKOP-16-2017-00009) Támogató: EFOP-VEKOP </div>
<div class="lastModified">Utolsó módosítás: 2023.09.02. 17:32 Milánkovics Róbert (PTE ÁOK admin 4)
</div>
<pre class="comment" style="margin-top: 0; margin-bottom: 0;"><u>Megjegyzés</u>: * Megosztott szerzőség</pre>
</div></div>
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First Department of Medicine, University of Szeged, Szeged, Hungary
HAS-USZ Momentum Epithelial Cell Signaling and Secretion Research Group, University of Szeged, Szeged, Hungary
Department of Pathophysiology, University of Szeged, Szeged, Hungary
HAS-USZ Momentum Translational Gastroenterology Research Group, University of Szeged, Szeged, Hungary
Institute for Translational Medicine and First Department Medicine, Medical School, University of Pécs, Pécs, Hungary
Department of Public Health, University of Szeged, Szeged, Hungary
Cited By :22
Export Date: 26 January 2024
CODEN: LAINA
Correspondence Address: Maléth, J.; First Department of Medicine, Hungary; email: maleth.jozsef@med.u-szeged-hu
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Pancreatic exocrine secretory processes are challenging to investigate on primary epithelial cells. Pancreatic organoid cultures may help to overcome shortcomings of the current models, however the ion secretory processes in pancreatic organoids-and therefore their physiological relevance or their utility in disease modeling-are not known. To answer these questions, we provide side-by-side comparison of gene expression, morphology, and function of epithelial cells in primary isolated pancreatic ducts and organoids. We used mouse pancreatic ductal fragments for experiments or were grown in Matrigel to obtain organoid cultures. Using PCR analysis we showed that gene expression of ion channels and transporters remarkably overlap in primary ductal cells and organoids. Morphological analysis with scanning electron microscopy revealed that pancreatic organoids form polarized monolayers with brush border on the apical membrane. Whereas the expression and localization of key proteins involved in ductal secretion (cystic fibrosis transmembrane conductance regulator, Na+/H+ exchanger 1 and electrogenic Na+/HCO3- cotransporter 1) are equivalent to the primary ductal fragments. Measurements of intracellular pH and Cl- levels revealed no significant difference in the activities of the apical Cl-/HCO3- exchange, or in the basolateral Na+ dependent HCO3- uptake. In summary we found that ion transport activities in the mouse pancreatic organoids are remarkably similar to those observed in freshly isolated primary ductal fragments. These results suggest that organoids can be suitable and robust model to study pancreatic ductal epithelial ion transport in health and diseases and facilitate drug development for secretory pancreatic disorders like cystic fibrosis, or chronic pancreatitis.
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<div class="JournalArticle Publication short-list"> <div class="authors"> <span class="author-name" mtid="10051983"> <a href="/gui2/?type=authors&mode=browse&sel=10051983" target="_blank">Molnár, Réka</a> </span> <span class="author-type"> </span> ; <span class="author-name" mtid="10059215"> <a href="/gui2/?type=authors&mode=browse&sel=10059215" target="_blank">Madácsy, Tamara</a> </span> <span class="author-type"> </span> ; <span class="author-name" mtid="10061075"> <a href="/gui2/?type=authors&mode=browse&sel=10061075" target="_blank">Varga, Árpád</a> </span> <span class="author-type"> </span> ; <span class="author-name" mtid="10058163"> <a href="/gui2/?type=authors&mode=browse&sel=10058163" target="_blank">Németh, Margit</a> </span> <span class="author-type"> </span> ; <span class="author-name" mtid="10059078"> <a href="/gui2/?type=authors&mode=browse&sel=10059078" target="_blank">Katona, Xénia</a> </span> <span class="author-type"> </span> ; <span class="author-name" mtid="10080809"> <a href="/gui2/?type=authors&mode=browse&sel=10080809" target="_blank">Görög, Marietta</a> </span> <span class="author-type"> </span> ; <span class="author-name" > Molnár, Brigitta </span> <span class="author-type"> </span> ; <span class="author-name" mtid="10054985"> <a href="/gui2/?type=authors&mode=browse&sel=10054985" target="_blank">Fanczal, Júlia</a> </span> <span class="author-type"> </span> ; <span class="author-name" mtid="10000098"> <a href="/gui2/?type=authors&mode=browse&sel=10000098" target="_blank">Rakonczay, Zoltán</a> </span> <span class="author-type"> </span> ; <span class="author-name" mtid="10002629"> <a href="/gui2/?type=authors&mode=browse&sel=10002629" target="_blank">Hegyi, Péter</a> </span> <span class="author-type"> </span> et al. </div ><div class="title"><a href="/gui2/?mode=browse¶ms=publication;30766190" mtid="30766190" target="_blank">Mouse pancreatic ductal organoid culture as a relevant model to study exocrine pancreatic ion secretion</a></div> <div class="pub-info"> <span class="journal-title">LABORATORY INVESTIGATION</span> <span class="journal-volume">100</span> : <span class="journal-issue">1</span> <span class="page"> pp. 84-97. , 14 p. </span> <span class="year">(2020)</span> </div> <div class="pub-end"><div class="identifier-list"> <span class="identifiers"> <span class="id identifier oa_GOLD" title=" Gold "> <a style="color:blue" title="10.1038/s41374-019-0300-3" target="_blank" href="https://doi.org/10.1038/s41374-019-0300-3"> DOI </a> </span> <span class="id identifier oa_GREEN" title=" Green "> <a style="color:black" title="101276" target="_blank" href="http://real.mtak.hu/101276"> REAL </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="000503181600008" target="_blank" href="https://www.webofscience.com/wos/woscc/full-record/000503181600008"> WoS </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="85070801321" target="_blank" href="http://www.scopus.com/record/display.url?origin=inward&eid=2-s2.0-85070801321"> Scopus </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="31409889" target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=31409889&dopt=Abstract"> PubMed </a> </span> <span class="id identifier oa_GREEN" title=" Green "> <a style="color:blue" title="16861" target="_blank" href="http://publicatio.bibl.u-szeged.hu/16861"> SZTE Publicatio </a> </span> </span> </div> <div class="short-pub-prop-list"> <span class="short-pub-mtid"> Közlemény:30766190 </span> <span class="status-holder"><span class="status-data status-VALIDATED"> Egyeztetett </span></span> <span class="pub-core">Forrás Idéző </span> <span class="pub-type">Folyóiratcikk (Szakcikk ) </span> <!-- && !record.category.scientific --> <span class="pub-category">Tudományos</span> <div class="publication-citation" style="margin-left: 0.5cm;"> <span title="Nyilvános idézőközlemények összesen, említések nélkül" class="citingPub-count">Nyilvános idéző összesen: 26</span> | Független: 14 | Függő: 12 | Nem jelölt: 0 | WoS jelölt: 26 | Scopus jelölt: 24 | WoS/Scopus jelölt: 26 | DOI jelölt: 24 </div> </div> </div> </div><div class="JournalArticle Publication long-list">
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<div class="autype autype0"> <span class="author-name" mtid="10051983"><a
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<span class="authorAux-mtmt"> Élettan</span>)
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<span class="author-affil"><span title="Szegedi Tudományegyetem">SZTE</span>/<span title="Általános Orvostudományi Kar">ÁOK</span>/<span title="Belgyógyászati Klinika">BK</span>/I. sz. Belgyógyászati Klinika</span>
;
<span class="author-name" mtid="10059215"><a
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</a>
</span>
<span class="author-affil"><span title="Szegedi Tudományegyetem">SZTE</span>/<span title="Általános Orvostudományi Kar">ÁOK</span>/<span title="Belgyógyászati Klinika">BK</span>/I. sz. Belgyógyászati Klinika; <span title="Szegedi Tudományegyetem">SZTE</span>/<span title="Általános Orvostudományi Kar">ÁOK</span>/<span title="Belgyógyászati Klinika">BK</span>/<span title="I. sz. Belgyógyászati Klinika">I.BelK</span>/MTA-SZTE Lendület Epitél Sejt Szignalizáció és Szekréció Kutatócsoport</span>
;
<span class="author-name" mtid="10061075"><a
href="/gui2/?type=authors&mode=browse&sel=10061075" target="_blank">Varga Árpád
(<span class="authorship-author-name">Varga Árpád</span>
<span class="authorAux-mtmt"> Sejt- és molekuláris biológia</span>)
</a>
</span>
<span class="author-affil"><span title="Szegedi Tudományegyetem">SZTE</span>/<span title="Általános Orvostudományi Kar">ÁOK</span>/<span title="Belgyógyászati Klinika">BK</span>/I. sz. Belgyógyászati Klinika; <span title="Szegedi Tudományegyetem">SZTE</span>/<span title="Általános Orvostudományi Kar">ÁOK</span>/<span title="Belgyógyászati Klinika">BK</span>/<span title="I. sz. Belgyógyászati Klinika">I.BelK</span>/MTA-SZTE Lendület Epitél Sejt Szignalizáció és Szekréció Kutatócsoport</span>
;
<span class="author-name" mtid="10058163"><a
href="/gui2/?type=authors&mode=browse&sel=10058163" target="_blank">Németh Margit
(<span class="authorship-author-name">Németh Margit</span>
<span class="authorAux-mtmt"> biológia</span>)
</a>
</span>
<span class="author-affil"><span title="Szegedi Tudományegyetem">SZTE</span>/<span title="Általános Orvostudományi Kar">ÁOK</span>/<span title="Belgyógyászati Klinika">BK</span>/I. sz. Belgyógyászati Klinika; <span title="Szegedi Tudományegyetem">SZTE</span>/<span title="Általános Orvostudományi Kar">ÁOK</span>/<span title="Belgyógyászati Klinika">BK</span>/<span title="I. sz. Belgyógyászati Klinika">I.BelK</span>/MTA-SZTE Lendület Epitél Sejt Szignalizáció és Szekréció Kutatócsoport</span>
;
<span class="author-name" mtid="10059078"><a
href="/gui2/?type=authors&mode=browse&sel=10059078" target="_blank">Katona Xénia
(<span class="authorship-author-name">Katona Xénia</span>
<span class="authorAux-mtmt"> neurobiológia</span>)
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</span>
<span class="author-affil"><span title="Szegedi Tudományegyetem">SZTE</span>/<span title="Általános Orvostudományi Kar">ÁOK</span>/<span title="Belgyógyászati Klinika">BK</span>/I. sz. Belgyógyászati Klinika; <span title="Szegedi Tudományegyetem">SZTE</span>/<span title="Általános Orvostudományi Kar">ÁOK</span>/<span title="Belgyógyászati Klinika">BK</span>/<span title="I. sz. Belgyógyászati Klinika">I.BelK</span>/MTA-SZTE Lendület Epitél Sejt Szignalizáció és Szekréció Kutatócsoport</span>
;
<span class="author-name" mtid="10080809"><a
href="/gui2/?type=authors&mode=browse&sel=10080809" target="_blank">Görög Marietta
(<span class="authorship-author-name">Görög Marietta</span>
<span class="authorAux-mtmt"> belgyógyászat</span>)
</a>
</span>
<span class="author-affil"><span title="Szegedi Tudományegyetem">SZTE</span>/<span title="Általános Orvostudományi Kar">ÁOK</span>/<span title="Belgyógyászati Klinika">BK</span>/I. sz. Belgyógyászati Klinika; <span title="Szegedi Tudományegyetem">SZTE</span>/<span title="Általános Orvostudományi Kar">ÁOK</span>/<span title="Belgyógyászati Klinika">BK</span>/<span title="I. sz. Belgyógyászati Klinika">I.BelK</span>/MTA-SZTE Lendület Epitél Sejt Szignalizáció és Szekréció Kutatócsoport</span>
;
<span class="author-name" >Molnár Brigitta
</span>
;
<span class="author-name" mtid="10054985"><a
href="/gui2/?type=authors&mode=browse&sel=10054985" target="_blank">Fanczal Júlia
(<span class="authorship-author-name">Fanczal Júlia</span>
<span class="authorAux-mtmt"> pancreatitis (alapkutatás)</span>)
</a>
</span>
<span class="author-affil"><span title="Szegedi Tudományegyetem">SZTE</span>/<span title="Általános Orvostudományi Kar">ÁOK</span>/<span title="Belgyógyászati Klinika">BK</span>/<span title="I. sz. Belgyógyászati Klinika">I.BelK</span>/MTA-SZTE Lendület Epitél Sejt Szignalizáció és Szekréció Kutatócsoport</span>
;
<span class="author-name" mtid="10000098"><a
href="/gui2/?type=authors&mode=browse&sel=10000098" target="_blank">Rakonczay Zoltán
(<span class="authorship-author-name">Rakonczay Zoltán</span>
<span class="authorAux-mtmt"> Gasztroenterológia</span>)
</a>
</span>
<span class="author-affil"><span title="Szegedi Tudományegyetem">SZTE</span>/<span title="Általános Orvostudományi Kar">ÁOK</span>/Kórélettani Intézet</span>
;
<span class="author-name" mtid="10002629"><a
href="/gui2/?type=authors&mode=browse&sel=10002629" target="_blank">Hegyi Péter
(<span class="authorship-author-name">Hegyi Péter</span>
<span class="authorAux-mtmt"> Gasztroenterológia</span>)
</a>
</span>
<span class="author-affil"><span title="Pécsi Tudományegyetem">PTE</span>/<span title="Általános Orvostudományi Kar">ÁOK</span>/I.sz. Belgyógyászati Klinika; <span title="Szegedi Tudományegyetem">SZTE</span>/<span title="Általános Orvostudományi Kar">ÁOK</span>/<span title="Belgyógyászati Klinika">BK</span>/<span title="I. sz. Belgyógyászati Klinika">I.BelK</span>/MTA-SZTE Lendület Gasztroenterológiai Multidiszciplináris Kutatócsoport; <span title="Pécsi Tudományegyetem">PTE</span>/<span title="Általános Orvostudományi Kar">ÁOK</span>/Transzlációs Medicina Intézet</span>
;
<span class="author-name" mtid="10030075"><a
href="/gui2/?type=authors&mode=browse&sel=10030075" target="_blank">Pallagi Petra
(<span class="authorship-author-name">Pallagi Petra</span>
<span class="authorAux-mtmt"> Gasztroenterológia</span>)
</a>
</span>
<span class="author-affil"><span title="Szegedi Tudományegyetem">SZTE</span>/<span title="Általános Orvostudományi Kar">ÁOK</span>/<span title="Belgyógyászati Klinika">BK</span>/I. sz. Belgyógyászati Klinika; <span title="Szegedi Tudományegyetem">SZTE</span>/<span title="Általános Orvostudományi Kar">ÁOK</span>/<span title="Belgyógyászati Klinika">BK</span>/<span title="I. sz. Belgyógyászati Klinika">I.BelK</span>/MTA-SZTE Lendület Epitél Sejt Szignalizáció és Szekréció Kutatócsoport</span>
;
<span class="author-name" mtid="10030084"><a
href="/gui2/?type=authors&mode=browse&sel=10030084" target="_blank">Maléth József ✉
(<span class="authorship-author-name">Maléth József</span>
<span class="authorAux-mtmt"> Gasztroenterológia</span>)
</a>
</span>
<span class="author-affil"><span title="Szegedi Tudományegyetem">SZTE</span>/<span title="Általános Orvostudományi Kar">ÁOK</span>/<span title="Belgyógyászati Klinika">BK</span>/I. sz. Belgyógyászati Klinika; <span title="Szegedi Tudományegyetem">SZTE</span>/<span title="Általános Orvostudományi Kar">ÁOK</span>/Népegészségtani Intézet; <span title="Szegedi Tudományegyetem">SZTE</span>/<span title="Általános Orvostudományi Kar">ÁOK</span>/<span title="Belgyógyászati Klinika">BK</span>/<span title="I. sz. Belgyógyászati Klinika">I.BelK</span>/MTA-SZTE Lendület Epitél Sejt Szignalizáció és Szekréció Kutatócsoport</span>
</div>
</div>
<div class="title"><a href="/gui2/?mode=browse¶ms=publication;30766190" target="_blank">Mouse pancreatic ductal organoid culture as a relevant model to study exocrine pancreatic ion secretion</a></div> <div> <span class="journal-title">LABORATORY INVESTIGATION</span>
<span class="journal-issn">(<a target="_blank" href="https://portal.issn.org/resource/ISSN/0023-6837">0023-6837</a> <a target="_blank" href="https://portal.issn.org/resource/ISSN/1530-0307">1530-0307</a>)</span>:
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<div class="mtid"><span class="long-pub-mtid">Közlemény: 30766190</span>
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<div class="funder"> EMBERI ERŐFORRÁS FEJLESZTÉSI OPERATÍV PROGRAM (EFOP)(EFOP-3.6.2-162017-00006) Támogató: NKFIH, Smart rendszerek. Új Nemzeti Kiválóság Program(20391-3/2018/FEKUSTRAT) Támogató: EMMI, (UNKP-18-4-SZTE-85), (UNKP-18-3-I-SZTE-66), Az orvos-, egészségtudományi- és gyógyszerészképzés tudományos műhelyeinek fejlesztése(EFOP-3.6.3-VEKOP-16-2017-00009) Támogató: EFOP-VEKOP, (LP2017–18/2017) Támogató: MTA, (BO/00440/16/5) Támogató: MTA Bolyai pályázat, (BO/00569/17) Támogató: MTA Bolyai pályázat, GINOP - STAY ALIVE(GINOP-2.3.2-15-2016-00048) Támogató: Nemzeti Kutatási, Fejlesztési és Innovációs Hivatal, (PD116553), (K119938) </div>
<div class="lastModified">Utolsó módosítás: 2023.09.02. 17:27 Milánkovics Róbert (PTE ÁOK admin 4)
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<pre class="comment" style="margin-top: 0; margin-bottom: 0;"><u>Megjegyzés</u>: First Department of Medicine, University of Szeged, Szeged, Hungary
HAS-USZ Momentum Epithelial Cell Signaling and Secretion Research Group, University of Szeged, Szeged, Hungary
Department of Pathophysiology, University of Szeged, Szeged, Hungary
HAS-USZ Momentum Translational Gastroenterology Research Group, University of...</pre>
</div></div>
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The Epithelial Signaling and Transport Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, United States
First Department of Medicine, University of Szeged, Szeged, Hungary
Trans-NIH Shared Resource on Biomedical Engineering and Physical Science (BEPS) National Institute of Biomedical Imaging & Bioengineering, Bethesda, MD, United States
Export Date: 15 July 2019
CODEN: EMJOD
Correspondence Address: Muallem, S.; The Epithelial Signaling and Transport Section, National Institute of Dental and Craniofacial Research, National Institutes of HealthUnited States; email: shmuel.muallem@nih.gov
Funding details: Yale University
Funding details: Semmelweis Egyetem, Hungary
Funding details: DE000735-07
Funding details: University of Rochester, mCherry-PMCA4
Funding text 1: We thank Drs. James Rothman (Yale University), Agnes Enyedi (Semmelweis University, Budapest, Hungary), and David Yule (Rochester University) for providing plasmids for Ist2, mCherry-PMCA4, and mCherry-IP3R3, respectively. This work was funded by intramural grant from NIH/NIDCR DE000735-07.
The Epithelial Signaling and Transport Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, United States
First Department of Medicine, University of Szeged, Szeged, Hungary
Trans-NIH Shared Resource on Biomedical Engineering and Physical Science (BEPS) National Institute of Biomedical Imaging & Bioengineering, Bethesda, MD, United States
Cited By :2
Export Date: 17 October 2019
CODEN: EMJOD
Correspondence Address: Muallem, S.; The Epithelial Signaling and Transport Section, National Institute of Dental and Craniofacial Research, National Institutes of HealthUnited States; email: shmuel.muallem@nih.gov
Chemicals/CAS: adenosine triphosphatase, 37289-25-1, 9000-83-3; calcium ion, 14127-61-8
Funding details: DE000735-07
Funding text 1: We thank Drs. James Rothman (Yale University), Agnes Enyedi (Semmelweis University, Budapest, Hungary), and David Yule (Rochester University) for providing plasmids for Ist2, mCherry-PMCA4, and mCherry-IP3R3, respectively. This work was funded by intramural grant from NIH/NIDCR DE000735-07.
The Epithelial Signaling and Transport Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, United States
First Department of Medicine, University of Szeged, Szeged, Hungary
Trans-NIH Shared Resource on Biomedical Engineering and Physical Science (BEPS) National Institute of Biomedical Imaging & Bioengineering, Bethesda, MD, United States
Cited By :2
Export Date: 2 January 2020
CODEN: EMJOD
Correspondence Address: Muallem, S.; The Epithelial Signaling and Transport Section, National Institute of Dental and Craniofacial Research, National Institutes of HealthUnited States; email: shmuel.muallem@nih.gov
Chemicals/CAS: adenosine triphosphatase, 37289-25-1, 9000-83-3; calcium ion, 14127-61-8
Funding details: DE000735-07
Funding text 1: We thank Drs. James Rothman (Yale University), Agnes Enyedi (Semmelweis University, Budapest, Hungary), and David Yule (Rochester University) for providing plasmids for Ist2, mCherry-PMCA4, and mCherry-IP3R3, respectively. This work was funded by intramural grant from NIH/NIDCR DE000735-07.
Journal Article; Research Support, N.I.H., Intramural
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Communication and material transfer between membranes and organelles take place at membrane contact sites (MCSs). MCSs between the ER and PM, the ER/PM junctions, are the sites where the ER Ca2+ sensor STIM1 and the PM Ca2+ influx channel Orai1 cluster. MCSs are formed by tether proteins that bridge the opposing membranes, but the identity and role of these tethers in receptor-evoked Ca2+ signaling is not well understood. Here, we identified Anoctamin 8 (ANO8) as a key tether in the formation of the ER/PM junctions that is essential for STIM1-STIM1 interaction and STIM1-Orai1 interaction and channel activation at a ER/PM PI(4,5)P2-rich compartment. Moreover, ANO8 assembles all core Ca2+ signaling proteins: Orai1, PMCA, STIM1, IP3 receptors, and SERCA2 at the ER/PM junctions to mediate a novel form of Orai1 channel inactivation by markedly facilitating SERCA2-mediated Ca2+ influx into the ER. This controls the efficiency of receptor-stimulated Ca2+ signaling, Ca2+ oscillations, and duration of Orai1 activity to prevent Ca2+ toxicity. These findings reveal the central role of MCSs in determining efficiency and fidelity of cell signaling. © 2019 The Authors
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<pre class="comment" style="margin-top: 0; margin-bottom: 0;"><u>Megjegyzés</u>: The Epithelial Signaling and Transport Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, United States
First Department of Medicine, University of Szeged, Szeged, Hungary
Trans-NIH Shared Resource on Biomedical Engineering and Physical Science (BEPS) National Institute of Biomedical Imagi...</pre>
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Epithelial Signaling and Transport Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, United States
Genetics and Pathogenesis of Allergy Section, Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United States
HAS-USZ Momentum Epithelial Cell Signaling and Secretion Research Group, First Department of Medicine, University of Szeged, Szeged, Hungary
NIDCR imaging core, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, United States
Department of Oral Biology, BK 21 PLUS Project, Yonsei University College of Dentistry, Seoul, South Korea
Export Date: 2 January 2020
CODEN: GASTA
Correspondence Address: Muallem, S.; Epithelial Signaling and Transport Section, National Institute of Dental and Craniofacial Research, NIHUnited States; email: Shmuel.muallem@nih.gov
Chemicals/CAS: amylase, 9000-90-2, 9000-92-4, 9001-19-8; arginine, 1119-34-2, 15595-35-4, 7004-12-8, 74-79-3; carbachol, 462-58-8, 51-83-2; ceruletide, 17650-98-5; hemagglutinin, 37333-12-3
Funding details: LP2017-18/2017
Funding details: Ministry of Science ICT and Future Planning, MSIP, 2016R1A5A2008630
Funding details: Foundation for the National Institutes of Health, FNIH, DE DE000735-08
Funding details: 20391-3/2018/FEKUSTRAT
Funding details: National Research Foundation of Korea, NRF
Funding text 1: Funding Funded by National Institutes of Health intramural grant DE DE000735-08 to Shmuel Muallem. Jozsef Maleth was funded by the Hungarian Academy of Science (LP2017-18/2017) and by the National Excellence Programme (20391-3/2018/FEKUSTRAT). Dong Min Shin was funded by a National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIP) (NRF. 2016R1A5A2008630).
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<div class="JournalArticle Publication short-list"> <div class="authors"> <span class="author-name" > Son, Aran </span> <span class="author-type"> </span> ; <span class="author-name" > Ahuja, Malini </span> <span class="author-type"> </span> ; <span class="author-name" > Schwartz, Daniella M. </span> <span class="author-type"> </span> ; <span class="author-name" mtid="10061075"> <a href="/gui2/?type=authors&mode=browse&sel=10061075" target="_blank">Varga, Arpad</a> </span> <span class="author-type"> </span> ; <span class="author-name" > Swaim, William </span> <span class="author-type"> </span> ; <span class="author-name" > Kang, Namju </span> <span class="author-type"> </span> ; <span class="author-name" mtid="10030084"> <a href="/gui2/?type=authors&mode=browse&sel=10030084" target="_blank">Maleth, Jozsef</a> </span> <span class="author-type"> </span> ; <span class="author-name" > Shin, Dong Min </span> <span class="author-type"> </span> ; <span class="author-name" > Muallem, Shmuel ✉ </span> <span class="author-type"> </span> </div ><div class="title"><a href="/gui2/?mode=browse¶ms=publication;30799285" mtid="30799285" target="_blank">Ca2+ Influx Channel Inhibitor SARAF Protects Mice From Acute Pancreatitis</a></div> <div class="pub-info"> <span class="journal-title">GASTROENTEROLOGY</span> <span class="journal-volume">157</span> : <span class="journal-issue">6</span> <span class="page"> pp. 1660-1672.e2. , 13 p. </span> <span class="year">(2019)</span> </div> <div class="pub-end"><div class="identifier-list"> <span class="identifiers"> <span class="id identifier oa_PAY" title=" Fizetős "> <a style="color:blue" title="10.1053/j.gastro.2019.08.042" target="_blank" href="https://doi.org/10.1053/j.gastro.2019.08.042"> DOI </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="000498848300034" target="_blank" href="https://www.webofscience.com/wos/woscc/full-record/000498848300034"> WoS </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="85075218267" target="_blank" href="http://www.scopus.com/record/display.url?origin=inward&eid=2-s2.0-85075218267"> Scopus </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="31493399" target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=31493399&dopt=Abstract"> PubMed </a> </span> <span class="id identifier oa_GREEN" title=" Green "> <a style="color:blue" title="17962" target="_blank" href="http://publicatio.bibl.u-szeged.hu/17962"> SZTE Publicatio </a> </span> </span> </div> <div class="short-pub-prop-list"> <span class="short-pub-mtid"> Közlemény:30799285 </span> <span class="status-holder"><span class="status-data status-VALIDATED"> Egyeztetett </span></span> <span class="pub-core">Forrás Idéző </span> <span class="pub-type">Folyóiratcikk (Szakcikk ) </span> <!-- && !record.category.scientific --> <span class="pub-category">Tudományos</span> <div class="publication-citation" style="margin-left: 0.5cm;"> <span title="Nyilvános idézőközlemények összesen, említések nélkül" class="citingPub-count">Nyilvános idéző összesen: 32</span> | Független: 28 | Függő: 4 | Nem jelölt: 0 | WoS jelölt: 25 | Scopus jelölt: 29 | WoS/Scopus jelölt: 30 | DOI jelölt: 32 (Nem nyilvános: 1) </div> </div> </div> </div><div class="JournalArticle Publication long-list">
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<span class="author-name" >Ahuja Malini
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<span class="author-name" >Schwartz Daniella M.
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<span class="authorAux-mtmt"> Sejt- és molekuláris biológia</span>)
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<span class="author-name" mtid="10030084"><a
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<span class="author-affil"><span title="Szegedi Tudományegyetem">SZTE</span>/<span title="Általános Orvostudományi Kar">ÁOK</span>/I. sz. Belgyógyászati Klinika; <span title="Szegedi Tudományegyetem">SZTE</span>/<span title="Általános Orvostudományi Kar">ÁOK</span>/<span title="I. sz. Belgyógyászati Klinika">I.BelK</span>/MTA-SZTE Lendület Epitél Sejt Szignalizáció és Szekréció Kutatócsoport</span>
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<span class="author-name" >Shin Dong Min
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<span class="author-name" >Muallem Shmuel ✉
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<div class="title"><a href="/gui2/?mode=browse¶ms=publication;30799285" target="_blank">Ca2+ Influx Channel Inhibitor SARAF Protects Mice From Acute Pancreatitis</a></div> <div> <span class="journal-title">GASTROENTEROLOGY</span>
<span class="journal-issn">(<a target="_blank" href="https://portal.issn.org/resource/ISSN/0016-5085">0016-5085</a> <a target="_blank" href="https://portal.issn.org/resource/ISSN/1528-0012">1528-0012</a>)</span>:
<span class="journal-volume">157</span> <span class="journal-issue">6</span>
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pp 1660-1672.e2
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<a style="color:blue" title="10.1053/j.gastro.2019.08.042" target="_blank" href="https://doi.org/10.1053/j.gastro.2019.08.042">
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<span title="Nyilvános idézőközlemények összesen, említések nélkül" class="citingPub-count">Nyilvános idéző összesen: 32</span>
| Független: 28
| Függő: 4
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Idézett közlemények száma: 7
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<div class="mtid"><span class="long-pub-mtid">Közlemény: 30799285</span>
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Forrás Idéző
| <span class="type-subtype">Folyóiratcikk
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<div class="lastModified">Utolsó módosítás: 2021.11.28. 17:36 Bernátskyné Babus Csilla (SZTE admin4)
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<pre class="comment" style="margin-top: 0; margin-bottom: 0;"><u>Megjegyzés</u>: Epithelial Signaling and Transport Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, United States
Genetics and Pathogenesis of Allergy Section, Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United States
...</pre>
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Epithelial cells line the entire surface of the gastrointestinal tract and its accessory organs where they primarily function in transporting digestive enzymes, nutrients, electrolytes, and fluid to and from the luminal contents. At the same time, epithelial cells are responsible for forming a physical and biochemical barrier that prevents the entry into the body of harmful agents, such as bacteria and their toxins. Dysregulation of epithelial transport and barrier function is associated with the pathogenesis of a number of conditions throughout the intestine, such as inflammatory bowel disease, chronic diarrhea, pancreatitis, reflux esophagitis, and cancer. Driven by discovery of specific receptors on intestinal epithelial cells, new insights into mechanisms that control their synthesis and enterohepatic circulation, and a growing appreciation of their roles as bioactive bacterial metabolites, bile acids are currently receiving a great deal of interest as critical regulators of epithelial function in health and disease. This review aims to summarize recent advances in this field and to highlight how bile acids are now emerging as exciting new targets for disease intervention.
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<div class="JournalArticle Publication short-list"> <div class="authors"> <span class="author-name" mtid="10002629"> <a href="/gui2/?type=authors&mode=browse&sel=10002629" target="_blank">Hegyi, P</a> </span> <span class="author-type"> </span> ; <span class="author-name" mtid="10030084"> <a href="/gui2/?type=authors&mode=browse&sel=10030084" target="_blank">Maleth, J</a> </span> <span class="author-type"> </span> ; <span class="author-name" > Walters, JR </span> <span class="author-type"> </span> ; <span class="author-name" > Hofmann, AF </span> <span class="author-type"> </span> ; <span class="author-name" > Keely, SJ ✉ </span> <span class="author-type"> </span> </div ><div class="title"><a href="/gui2/?mode=browse¶ms=publication;3401783" mtid="3401783" target="_blank">Guts and Gall: Bile Acids in Regulation of Intestinal Epithelial Function in Health and Disease.</a></div> <div class="pub-info"> <span class="journal-title">PHYSIOLOGICAL REVIEWS</span> <span class="journal-volume">98</span> : <span class="journal-issue">4</span> <span class="page"> pp. 1983-2023. , 41 p. </span> <span class="year">(2018)</span> </div> <div class="pub-end"><div class="identifier-list"> <span class="identifiers"> <span class="id identifier oa_GOLD" title=" Gold "> <a style="color:blue" title="10.1152/physrev.00054.2017" target="_blank" href="https://doi.org/10.1152/physrev.00054.2017"> DOI </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="000441186400003" target="_blank" href="https://www.webofscience.com/wos/woscc/full-record/000441186400003"> WoS </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="85055615852" target="_blank" href="http://www.scopus.com/record/display.url?origin=inward&eid=2-s2.0-85055615852"> Scopus </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="30067158" target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=30067158&dopt=Abstract"> PubMed </a> </span> <span class="id identifier oa_GREEN" title=" Green "> <a style="color:blue" title="14582" target="_blank" href="http://publicatio.bibl.u-szeged.hu/14582"> SZTE Publicatio </a> </span> </span> </div> <div class="short-pub-prop-list"> <span class="deleted-record">Zárolt</span> <span class="short-pub-mtid"> Közlemény:3401783 </span> <span class="status-holder"><span class="status-data status-CHECKED"> Hitelesített </span></span> <span class="pub-core">Forrás Idéző </span> <span class="pub-type">Folyóiratcikk (Összefoglaló cikk ) </span> <!-- && !record.category.scientific --> <span class="pub-category">Tudományos</span> <div class="publication-citation" style="margin-left: 0.5cm;"> <span title="Nyilvános idézőközlemények összesen, említések nélkül" class="citingPub-count">Nyilvános idéző összesen: 206</span> | Független: 199 | Függő: 7 | Nem jelölt: 0 | WoS jelölt: 170 | Scopus jelölt: 171 | WoS/Scopus jelölt: 186 | DOI jelölt: 176 </div> </div> </div> </div><div class="JournalArticle Publication long-list"> <div class="authors"> <img title="Forrásközlemény" style="float: left" src="/frontend/resources/grid/publication-core-icon.png"> <img title="Idézőközlemény" style="float: left" src="/frontend/resources/grid/publication-citation-icon.png"> <div class="autype autype0"> <span class="author-name" mtid="10002629"><a href="/gui2/?type=authors&mode=browse&sel=10002629" target="_blank">Hegyi P (<span class="authorship-author-name">Hegyi Péter</span> <span class="authorAux-mtmt"> Gasztroenterológia</span>) </a> </span> <span class="author-affil"><span title="Szegedi Tudományegyetem">SZTE</span>/<span title="Általános Orvostudományi Kar">ÁOK</span>/<span title="I. sz. 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Belgyógyászati Klinika">I.BelK</span>/MTA-SZTE Lendület Epitél Sejt Szignalizáció és Szekréció Kutatócsoport</span> ; <span class="author-name" >Walters JR </span> ; <span class="author-name" >Hofmann AF </span> ; <span class="author-name" >Keely SJ ✉ </span> </div> </div> <div class="title"><a href="/gui2/?mode=browse¶ms=publication;3401783" target="_blank">Guts and Gall: Bile Acids in Regulation of Intestinal Epithelial Function in Health and Disease.</a></div> <div> <span class="journal-title">PHYSIOLOGICAL REVIEWS</span> <span class="journal-issn">(<a target="_blank" href="https://portal.issn.org/resource/ISSN/0031-9333">0031-9333</a> <a target="_blank" href="https://portal.issn.org/resource/ISSN/1522-1210">1522-1210</a>)</span>: <span class="journal-volume">98</span> <span class="journal-issue">4</span> <span class="page"> pp 1983-2023 </span> <span class="year">(2018)</span> </div> <div class="pub-footer"> <span class="language" xmlns="http://www.w3.org/1999/html">Nyelv: Angol | </span> <span class="identifiers"> <span class="id identifier oa_GOLD" title=" Gold "> <a style="color:blue" title="10.1152/physrev.00054.2017" target="_blank" href="https://doi.org/10.1152/physrev.00054.2017"> DOI </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="000441186400003" target="_blank" href="https://www.webofscience.com/wos/woscc/full-record/000441186400003"> WoS </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="85055615852" target="_blank" href="http://www.scopus.com/record/display.url?origin=inward&eid=2-s2.0-85055615852"> Scopus </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="30067158" target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=30067158&dopt=Abstract"> PubMed </a> </span> <span class="id identifier oa_GREEN" title=" Green "> <a style="color:blue" title="14582" target="_blank" href="http://publicatio.bibl.u-szeged.hu/14582"> SZTE Publicatio </a> </span> </span> <div class="publication-citation" style="margin-left: 0.5cm;"> <span title="Nyilvános idézőközlemények összesen, említések nélkül" class="citingPub-count">Nyilvános idéző összesen: 206</span> | Független: 199 | Függő: 7 | Nem jelölt: 0 | WoS jelölt: 170 | Scopus jelölt: 171 | WoS/Scopus jelölt: 186 | DOI jelölt: 176 </div> <div class="publication-citation"> <a target="_blank" href="/api/publication?cond=citations.related;eq;3401783&sort=publishedYear,desc&sort=title"> Idézett közlemények száma: 11 </a> </div> <div class="mtid"><span class="long-pub-mtid">Közlemény: 3401783</span> | <span class="status-data status-CHECKED"> Hitelesített </span> <span class="oldId">Régi azonosító: 3401783</span> | Forrás Idéző | <span class="type-subtype">Folyóiratcikk ( Összefoglaló cikk ) </span> | <span class="pub-category">Tudományos</span> | <span class="publication-sourceOfData">MEDLINE</span> </div> <div class="lastModified">Utolsó módosítás: 2021.11.28. 17:16 Bernátskyné Babus Csilla (SZTE admin4) </div> <div class="lockedBy">Zárolva 2021.11.28. 17:16 Bernátskyné Babus Csilla (SZTE admin4)</div> <div class="lockedBy">Hitelesítő 2021.11.28. 17:16 Bernátskyné Babus Csilla (SZTE admin4)</div> </div></div>