https://m2.mtmt.hu/ eng 2026-04-17 09:16 JournalArticle 32800045 VALIDATED true 0 false 2026-04-10T07:32:37.782+0000 2026-02-09T08:42:36.833+0000 2022-04-29T12:38:15.164+0000 true 10039043 Milánkovics Róbert /api/admin/10039043 Admin true 10039043 2026-02-09T08:42:37.272+0000 2026-02-09T08:42:37.272+0000 2024-11-28T06:00:39.586+0000 true 10039043 Milánkovics Róbert /api/admin/10039043 Admin true 10039043 Admin 10003134 /api/admin/10003134 Wolf György true 10003134 true 2026-02-03T09:39:04.200+0000 true false true 24 24 /api/publicationtype/24 PublicationType 1 true 24 JournalArticle true 10000059 Article true 24 24 /api/publicationtype/24 PublicationType 1 true 24 JournalArticle /api/subtype/10000059 Szakcikk SubType 101 true 10000059 true 1 /api/category/1 Category true 1 Madácsy, Tamara Impaired regulation of PMCA activity by defective CFTR expression promotes epithelial cell damage in alcoholic pancreatitis and hepatitis true true /api/journal/11507 REVIEWED true false 11507 false 11507 true 1420-682X 1420-9071 Journal FOREIGN 79 5 265 265 18 2022 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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Sz. Gyermekgyógyászati Klinika (SE / AOK / K); I. sz. Belgyógyászati Klinika (SZTE / SZAOK / BK); Kórélettani Intézet (SZTE / SZAOK); MTA-SZTE Lendület Epitél Sejt Szignalizáció és ... (SZTE / SZAOK / BK / I.BelK); MTA-SZTE Lendület Gasztroenterológiai Multidisz... 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Classification 12302 /api/classification/12302 true true Classification 12124 /api/classification/12124 true true Keyword 1022667 /api/keyword/1022667 true 1022667 true Keyword 1045754 /api/keyword/1045754 true 1045754 true Keyword 1057133 /api/keyword/1057133 true 1057133 true Keyword 1414004 /api/keyword/1414004 true 1414004 true Keyword 2621819 /api/keyword/2621819 true true SjrRating 11285533 /api/sjrrating/11285533 15 0.1 journal RatingType 10002 /api/ratingtype/10002 sjr true true ClassificationExternal 1313 /api/classificationexternal/1313 true 1313 true D1 DIRECT true true /api/publication/32800045 <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="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="University of Szeged">SZTE</span>/<span title="Albert Szent-Györgyi Medical School">ASZMS</span>/<span title="Department of Internal Medicine">DIMedicine</span>/First Department of Internal Medicine; <span title="University of Szeged">SZTE</span>/<span title="Albert Szent-Györgyi Medical School">ASZMS</span>/<span title="Department of Internal Medicine">DIMedicine</span>/<span title="First Department of Internal Medicine">I.DIM</span>/MTA-SZTE Momentum Epithelial Cell Signalling and Secretion Research Group</span> ;&nbsp;&nbsp;&nbsp; <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"> Gasztroenterológia</span>) </a> </span> <span class="author-affil"><span title="University of Szeged">SZTE</span>/<span title="Albert Szent-Györgyi Medical School">ASZMS</span>/<span title="Department of Internal Medicine">DIMedicine</span>/First Department of Internal Medicine; <span title="University of Szeged">SZTE</span>/<span title="Albert Szent-Györgyi Medical School">ASZMS</span>/<span title="Department of Internal Medicine">DIMedicine</span>/<span title="First Department of Internal Medicine">I.DIM</span>/MTA-SZTE Momentum Epithelial Cell Signalling and Secretion Research Group</span> ;&nbsp;&nbsp;&nbsp; <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="University of Szeged">SZTE</span>/<span title="Albert Szent-Györgyi Medical School">ASZMS</span>/<span title="Department of Internal Medicine">DIMedicine</span>/First Department of Internal Medicine; <span title="University of Szeged">SZTE</span>/<span title="Albert Szent-Györgyi Medical School">ASZMS</span>/<span title="Department of Internal Medicine">DIMedicine</span>/<span title="First Department of Internal Medicine">I.DIM</span>/MTA-SZTE Momentum Epithelial Cell Signalling and Secretion Research Group</span> ;&nbsp;&nbsp;&nbsp; <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 University">SU</span>/<span title="Faculty of Medicine">FM</span>/<span title="Clinical">C</span>/I. Department of Pediatrics; <span title="University of Szeged">SZTE</span>/<span title="Albert Szent-Györgyi Medical School">ASZMS</span>/<span title="Department of Internal Medicine">DIMedicine</span>/<span title="First Department of Internal Medicine">I.DIM</span>/MTA-SZTE Momentum Epithelial Cell Signalling and Secretion Research Group</span> ;&nbsp;&nbsp;&nbsp; <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="University of Szeged">SZTE</span>/<span title="Albert Szent-Györgyi Medical School">ASZMS</span>/<span title="Department of Internal Medicine">DIMedicine</span>/First Department of Internal Medicine; <span title="University of Szeged">SZTE</span>/<span title="Albert Szent-Györgyi Medical School">ASZMS</span>/<span title="Department of Internal Medicine">DIMedicine</span>/<span title="First Department of Internal Medicine">I.DIM</span>/MTA-SZTE Momentum Epithelial Cell Signalling and Secretion Research Group</span> ;&nbsp;&nbsp;&nbsp; <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>) </a> </span> <span class="author-affil"><span title="University of Szeged">SZTE</span>/<span title="Albert Szent-Györgyi Medical School">ASZMS</span>/<span title="Department of Internal Medicine">DIMedicine</span>/First Department of Internal Medicine; <span title="University of Szeged">SZTE</span>/<span title="Albert Szent-Györgyi Medical School">ASZMS</span>/<span title="Department of Internal Medicine">DIMedicine</span>/<span title="First Department of Internal Medicine">I.DIM</span>/MTA-SZTE Momentum Epithelial Cell Signalling and Secretion Research Group</span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" mtid="10078338"><a href="/gui2/?type=authors&mode=browse&sel=10078338" target="_blank">Kiss Aletta (<span class="authorship-author-name">Kiss Aletta Kata</span> <span class="authorAux-mtmt"> Sejt- és molekuláris biológia</span>) </a> </span> <span class="author-affil"><span title="University of Szeged">SZTE</span>/<span title="Albert Szent-Györgyi Medical School">ASZMS</span>/<span title="Department of Internal Medicine">DIMedicine</span>/<span title="First Department of Internal Medicine">I.DIM</span>/MTA-SZTE Momentum Epithelial Cell Signalling and Secretion Research Group; <span title="University of Szeged">SZTE</span>/<span title="Albert Szent-Györgyi Medical School">ASZMS</span>/<span title="Department of Internal Medicine">DIMedicine</span>/First Department of Internal Medicine</span> ;&nbsp;&nbsp;&nbsp; <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="University of Szeged">SZTE</span>/<span title="Albert Szent-Györgyi Medical School">ASZMS</span>/<span title="Department of Internal Medicine">DIMedicine</span>/First Department of Internal Medicine; <span title="University of Szeged">SZTE</span>/<span title="Albert Szent-Györgyi Medical School">ASZMS</span>/<span title="Department of Internal Medicine">DIMedicine</span>/<span title="First Department of Internal Medicine">I.DIM</span>/MTA-SZTE Momentum Epithelial Cell Signalling and Secretion Research Group</span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" mtid="10000098"><a href="/gui2/?type=authors&mode=browse&sel=10000098" target="_blank">Rakonczay Zoltan (<span class="authorship-author-name">Rakonczay Zoltán</span> <span class="authorAux-mtmt"> Gasztroenterológia</span>) </a> </span> <span class="author-affil"><span title="University of Szeged">SZTE</span>/<span title="Albert Szent-Györgyi Medical School">ASZMS</span>/Department of Pathophysiology</span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" mtid="10009640"><a href="/gui2/?type=authors&mode=browse&sel=10009640" target="_blank">Tiszlavicz László (<span class="authorship-author-name">Tiszlavicz László</span> <span class="authorAux-mtmt"> Pathológia</span>) </a> </span> <span class="author-affil"><span title="University of Szeged">SZTE</span>/<span title="Albert Szent-Györgyi Medical School">ASZMS</span>/Department of Pathology</span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" mtid="10023650"><a href="/gui2/?type=authors&mode=browse&sel=10023650" target="_blank">Rázga Zsolt (<span class="authorship-author-name">Rázga Zsolt</span> <span class="authorAux-mtmt"> Farmakológia, funkcionális morfológia</span>) </a> </span> <span class="author-affil"><span title="University of Szeged">SZTE</span>/<span title="Albert Szent-Györgyi Medical School">ASZMS</span>/Department of Pathology</span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >Hohwieler Meike </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >Kleger Alexander </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >Gray Mike </span> ;&nbsp;&nbsp;&nbsp; <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="Semmelweis University">SU</span>/<span title="Faculty of Medicine">FM</span>/<span title="Clinical">C</span>/Cardiovascular Center; <span title="University of Pécs">UP</span>/<span title="Medical School">UPMS</span>/Institute for Translational Medicine; <span title="Semmelweis University">SU</span>/<span title="Központi Szervezeti Egységek (beleértve az Egyéb Szervezeti Egységeket)">KSZE</span>/Centre for Translational Medicine; <span title="Semmelweis University">SU</span>/<span title="Faculty of Medicine">FM</span>/<span title="Clinical">C</span>/<span title="Cardiovascular Center">Cardiovascular Center</span>/Department of Pancreatic Diseases</span> ;&nbsp;&nbsp;&nbsp; <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="University of Szeged">SZTE</span>/<span title="Albert Szent-Györgyi Medical School">ASZMS</span>/<span title="Department of Internal Medicine">DIMedicine</span>/First Department of Internal Medicine; <span title="University of Szeged">SZTE</span>/<span title="Albert Szent-Györgyi Medical School">ASZMS</span>/<span title="Department of Internal Medicine">DIMedicine</span>/<span title="First Department of Internal Medicine">I.DIM</span>/MTA-SZTE Momentum Translational Gastroenterology Research Group; <span title="University of Szeged">SZTE</span>/<span title="Albert Szent-Györgyi Medical School">ASZMS</span>/<span title="Department of Internal Medicine">DIMedicine</span>/<span title="First Department of Internal Medicine">I.DIM</span>/MTA-SZTE Momentum Epithelial Cell Signalling and Secretion Research Group</span> </div> </div> <div class="title"><a href="/gui2/?mode=browse&params=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. </span> <span class="year">(2022)</span> </div> <div class="pub-footer"> <span class="language" xmlns="http://www.w3.org/1999/html">Language: English | </span> <span class="identifiers"> <span class="id identifier oa_PAY" title=" Pay "> <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> <OnlyViewableByAuthor><div class="ratings"> <div class="journal-subject">Journal subject: Scopus - Molecular Medicine&nbsp;&nbsp;&nbsp;Rank:&nbsp;D1</div> <div class="journal-subject">Journal subject: Scopus - Pharmacology&nbsp;&nbsp;&nbsp;Rank:&nbsp;D1</div> <div class="journal-subject">Journal subject: Scopus - Cell Biology&nbsp;&nbsp;&nbsp;Rank:&nbsp;Q1</div> <div class="journal-subject">Journal subject: Scopus - Cellular and Molecular Neuroscience&nbsp;&nbsp;&nbsp;Rank:&nbsp;Q1</div> <div class="journal-subject">Journal subject: Scopus - Molecular Biology&nbsp;&nbsp;&nbsp;Rank:&nbsp;Q1</div> </div></OnlyViewableByAuthor> <div class="publication-citation" style="margin-left: 0.5cm;"> <span title="" class="citingPub-count">Citing papers: 12</span> | Independent citation: 6 | Self citation: 6 | Unknown citation: 0 | Number of citations in WoS: 11 | Number of citations in Scopus:&nbsp;11 | WoS/Scopus assigned:&nbsp;11 | Number of citations with DOI:&nbsp;12 </div> <div class="publication-citation"> <a target="_blank" href="/api/publication?cond=citations.related;eq;32800045&sort=publishedYear,desc&sort=title"> Number of cited publications: 13 </a> </div> <div class="mtid"><span class="long-pub-mtid">Publication: 32800045</span> | <span class="status-data status-VALIDATED"> Validated </span> Core Citing | <span class="type-subtype">Journal Article ( Article ) </span> | <span class="pub-category">Scientific</span> | <span class="publication-sourceOfData">PubMed XML</span> </div> <div class="funder"> GINOP - STAY ALIVE(GINOP-2.3.2-15-2016-00048) Funder: Nemzeti Kutatási, Fejlesztési és Innovációs Hivatal, (PD116553), EMBERI ERŐFORRÁS FEJLESZTÉSI OPERATÍV PROGRAM (EFOP)(EFOP-3.6.2-162017-00006) Funder: NRDIO, (BO/00569/17) Funder: MTA Bolyai pályázat, (LP2017–18/2017) Funder: HAS, Smart rendszerek. Új Nemzeti Kiválóság Program(20391-3/2018/FEKUSTRAT) Funder: -, (TUDFO/47138-1/2019/ITM), Tématerületi Kiválósági Program 2021 - Transzlációs biomedicina(TKP2021-EGA-28) Funder: NRDIO, Új Nemzeti Kiválóság Program(UNKP-21-4-SZTE-116) Funder: NR-DIO, (ÚNKP-21-3-SZTE-68), Albert Szent-Györgyi Research Grant(5S 470 (A202)), HCEMM(739593) Funder: Horizon 2020, (NTP-NFTÖ-B-0011), (NTP-NFTÖ-21-B-0205), (NTP-NFTÖ-21-B-0079) </div> <div class="lastModified">Last Modified: 2026.02.09. 09:42 András Balázs (MTMT Központ, admin) </div> <div class="lockedBy">Centrally managed 2026.02.03. 10:39 György Wolf (MTMT Központi admin) </div> </div></div>