TY - JOUR AU - Petővári, Gábor AU - Tóth, Gábor AU - Turiák, Lilla AU - L. Kiss, Anna AU - Pálóczi, Krisztina AU - Sebestyén, Anna AU - Pesti, Adrián István AU - Kiss, András AU - Baghy, Kornélia AU - Dezső, Katalin AU - Füle, Tibor AU - Tátrai, Péter AU - Kovalszky, Ilona AU - Reszegi, Andrea TI - Dynamic Interplay in Tumor Ecosystems: Communication between Hepatoma Cells and Fibroblasts JF - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES J2 - INT J MOL SCI VL - 24 PY - 2023 IS - 18 PG - 26 SN - 1661-6596 DO - 10.3390/ijms241813996 UR - https://m2.mtmt.hu/api/publication/34156288 ID - 34156288 N1 - Funding Agency and Grant Number: Hungarian Scientific Research Fund [100904, 119283, 138593, FK-138763, 131603, K-142799, K-128881, PD-142418]; Semmelweis Scientific and Innovation Fund [STIA-KFI-2022]; National Research, Development, and Innovation Fund [UNKP-22-4-II-SE-9] Funding text: This research was funded by the Hungarian Scientific Research Fund (grants 100904 and 119283 to I.K.; grant 138593 to K.B.; grant FK-138763 to K.D.; grant 131603 to L.T.; grant K-142799 to A.S.; grant K-128881 to A.K.; and grant PD-142418 to G.P.); by the Semmelweis Scientific and Innovation Fund (STIA-KFI-2022 to A.R.); and by the National Research, Development, and Innovation Fund (UNKP-22-4-II-SE-9 New National Excellence Program of the Ministry of Human Capacities to G.P.). AB - Tumors are intricate ecosystems where cancer cells and non-malignant stromal cells, including cancer-associated fibroblasts (CAFs), engage in complex communication. In this study, we investigated the interaction between poorly (HLE) and well-differentiated (HuH7) hepatoma cells and LX2 fibroblasts. We explored various communication channels, including soluble factors, metabolites, extracellular vesicles (EVs), and miRNAs. Co-culture with HLE cells induced LX2 to produce higher levels of laminin β1, type IV collagen, and CD44, with pronounced syndecan-1 shedding. Conversely, in HuH7/LX2 co-culture, fibronectin, thrombospondin-1, type IV collagen, and cell surface syndecan-1 were dominant matrix components. Integrins α6β4 and α6β1 were upregulated in HLE, while α5β1 and αVβ1 were increased in HuH7. HLE-stimulated LX2 produced excess MMP-2 and 9, whereas HuH7-stimulated LX2 produced excess MMP-1. LX2 activated MAPK and Wnt signaling in hepatoma cells, and conversely, hepatoma-derived EVs upregulated MAPK and Wnt in LX2 cells. LX2-derived EVs induced over tenfold upregulation of SPOCK1/testican-1 in hepatoma EV cargo. We also identified liver cancer-specific miRNAs in hepatoma EVs, with potential implications for early diagnosis. In summary, our study reveals tumor type-dependent communication between hepatoma cells and fibroblasts, shedding light on potential implications for tumor progression. However, the clinical relevance of liver cancer-specific miRNAs requires further investigation. LA - English DB - MTMT ER - TY - JOUR AU - Műzes, Györgyi AU - L. Kiss, Anna AU - Tulassay, Zsolt AU - Sipos, Ferenc TI - Cell-free DNA-induced alteration of autophagy response and TLR9-signaling: their relation to amelioration of DSS-colitis JF - COMPARATIVE IMMUNOLOGY MICROBIOLOGY AND INFECTIOUS DISEASES J2 - COMP IMMUNOL MICROB VL - 52 PY - 2017 SP - 48 EP - 57 PG - 10 SN - 0147-9571 DO - 10.1016/j.cimid.2017.06.005 UR - https://m2.mtmt.hu/api/publication/3240602 ID - 3240602 LA - English DB - MTMT ER - TY - JOUR AU - Loscertales, Maria AU - Nicolaou, Fotini AU - Jeanne, Marion AU - Longoni, Mauro AU - Gould, Douglas B. AU - Sun, Yunwei AU - Maalouf, Faouzi I. AU - Nagy, Nándor AU - Donahoe, Patricia K. TI - Type IV collagen drives alveolar epithelial-endothelial association and the morphogenetic movements of septation (vol 14, 59, 2016) JF - BMC BIOLOGY J2 - BMC BIOL VL - 14 PY - 2016 PG - 3 SN - 1741-7007 DO - 10.1186/s12915-016-0297-7 UR - https://m2.mtmt.hu/api/publication/30982138 ID - 30982138 LA - English DB - MTMT ER - TY - JOUR AU - Várbíró, Szabolcs AU - Hadjadj, Leila AU - Ács, Nándor AU - Horvath, Eszter Mária AU - Heinzlmann, Andrea AU - Magyar, Attila AU - Tőkés, Anna-Mária AU - Patócs, Attila Balázs AU - Buday, Anna AU - Fekete, Andrea AU - Benyó, Zoltán AU - Nádasy, György László TI - Investigating the linkage between vitamin D and PCOS: development of new rat model JF - GYNECOLOGICAL ENDOCRINOLOGY J2 - GYNECOL ENDOCRINOL VL - 32 PY - 2016 IS - Suppl. 1 SP - 79 EP - 79 PG - 1 SN - 0951-3590 DO - 10.3109/09513590.2016.1150635 UR - https://m2.mtmt.hu/api/publication/3064983 ID - 3064983 LA - English DB - MTMT ER - TY - JOUR AU - Kántor, Orsolya AU - Mezey, Szilvia AU - Adeghate, Jennifer Oluyemisi AU - Naumann, A AU - Nitschke, R AU - Énzsöly, Anna AU - Szabó, Arnold AU - Lukáts, Ákos AU - Németh, János Tibor AU - Somogyvári, Zoltán AU - Völgyi, Béla TI - Calcium buffer proteins are specific markers of human retinal neurons. JF - CELL AND TISSUE RESEARCH J2 - CELL TISSUE RES VL - 365 PY - 2016 IS - 1 SP - 29 EP - 50 PG - 22 SN - 0302-766X DO - 10.1007/s00441-016-2376-z UR - https://m2.mtmt.hu/api/publication/3026433 ID - 3026433 AB - Ca2+-buffer proteins (CaBPs) modulate the temporal and spatial characteristics of transient intracellular Ca2+-concentration changes in neurons in order to fine-tune the strength and duration of the output signal. CaBPs have been used as neurochemical markers to identify and trace neurons of several brain loci including the mammalian retina. The CaBP content of retinal neurons, however, varies between species and, thus, the results inferred from animal models cannot be utilised directly by clinical ophthalmologists. Moreover, the shortage of well-preserved human samples greatly impedes human retina studies at the cellular and network level. Our purpose has therefore been to examine the distribution of major CaBPs, including calretinin, calbindin-D28, parvalbumin and the recently discovered secretagogin in exceptionally well-preserved human retinal samples. Based on a combination of immunohistochemistry, Neurolucida tracing and Lucifer yellow injections, we have established a database in which the CaBP marker composition can be defined for morphologically identified cell types of the human retina. Hence, we describe the full CaBP make-up for a number of human retinal neurons, including HII horizontal cells, AII amacrine cells, type-1 tyrosine-hydroxylase-expressing amacrine cells and other lesser known neurons. We have also found a number of unidentified cells whose morphology remains to be characterised. We present several examples of the colocalisation of two or three CaBPs with slightly different subcellular distributions in the same cell strongly suggesting a compartment-specific division of labour of Ca2+-buffering by CaBPs. Our work thus provides a neurochemical framework for future ophthalmological studies and renders new information concerning the cellular and subcellular distribution of CaBPs for experimental neuroscience. LA - English DB - MTMT ER - TY - JOUR AU - Schill, EM AU - Lake, JI AU - Tusheva, OA AU - Nagy, Nándor AU - Bery, SK AU - Foster, L AU - Avetisyan, M AU - Johnson, SL AU - Stenson, WF AU - Goldstein, AM AU - Heuckeroth, RO TI - Ibuprofen slows migration and inhibits bowel colonization by enteric nervous system precursors in zebrafish, chick and mouse. JF - DEVELOPMENTAL BIOLOGY J2 - DEV BIOL VL - 409 PY - 2016 IS - 2 SP - 473 EP - 488 PG - 16 SN - 0012-1606 DO - 10.1016/j.ydbio.2015.09.023 UR - https://m2.mtmt.hu/api/publication/3002750 ID - 3002750 N1 - Department of Pediatrics, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, United States Department of Pediatric Surgery, Massachusetts General Hospital, Harvard Medical School, 55 Fruit St., Boston, MA 02114, United States Department of Human Morphology and Developmental Biology, Faculty of Medicine, Semmelweis University, Budapest, Hungary Department of Pediatrics, The Children's Hospital of Philadelphia Research Inst, The Perelman School of Medicine at the Univ. of Pennsylvania, Abramson Research Center, Philadelphia, PA 19104, United States Department of Internal Medicine, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, United States Department of Genetics, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, United States Cited By :32 Export Date: 3 May 2022 CODEN: DEBIA Correspondence Address: Heuckeroth, R.O.; The Children's Hospital of Philadelphia Research Inst, Suite 1116I, 3615 Civic Center Blvd., United States; email: Heuckerothr@email.chop.edu Chemicals/CAS: ibuprofen, 15687-27-1, 79261-49-7, 31121-93-4, 527688-20-6; caspase 3, 169592-56-7; Caspase 3; Cyclooxygenase 1; Cyclooxygenase 2; Ibuprofen; Membrane Proteins; PPAR gamma; Ptgs1 protein, mouse; Ptgs2 protein, mouse; rac1 GTP-Binding Protein; rho-Associated Kinases AB - Hirschsprung Disease (HSCR) is a potentially deadly birth defect characterized by the absence of the enteric nervous system (ENS) in distal bowel. Although HSCR has clear genetic causes, no HSCR-associated mutation is 100% penetrant, suggesting gene-gene and gene-environment interactions determine HSCR occurrence. To test the hypothesis that certain medicines might alter HSCR risk we treated zebrafish with medications commonly used during early human pregnancy and discovered that ibuprofen caused HSCR-like absence of enteric neurons in distal bowel. Using fetal CF-1 mouse gut slice cultures, we found that ibuprofen treated enteric neural crest-derived cells (ENCDC) had reduced migration, fewer lamellipodia and lower levels of active RAC1/CDC42. Additionally, inhibiting ROCK, a RHOA effector and known RAC1 antagonist, reversed ibuprofen effects on migrating mouse ENCDC in culture. Ibuprofen also inhibited colonization of Ret+/- mouse bowel by ENCDC in vivo and dramatically reduced bowel colonization by chick ENCDC in culture. Interestingly, ibuprofen did not affect ENCDC migration until after at least three hours of exposure. Furthermore, mice deficient in Ptgs1 (COX 1) and Ptgs2 (COX 2) had normal bowel colonization by ENCDC and normal ENCDC migration in vitro suggesting COX-independent effects. Consistent with selective and strain specific effects on ENCDC, ibuprofen did not affect migration of gut mesenchymal cells, NIH3T3, or WT C57BL/6 ENCDC, and did not affect dorsal root ganglion cell precursor migration in zebrafish. Thus, ibuprofen inhibits ENCDC migration in vitro and bowel colonization by ENCDC in vivo in zebrafish, mouse and chick, but there are cell type and strain specific responses. These data raise concern that ibuprofen may increase Hirschsprung disease risk in some genetically susceptible children. LA - English DB - MTMT ER - TY - JOUR AU - Nagy, Nándor AU - Barad, Csilla Mária AU - Graham, HK AU - Hotta, R AU - Cheng, LS AU - Pecsenye-Fejszák, Nóra Florina AU - Goldstein, AM TI - Sonic hedgehog controls enteric nervous system development by patterning the extracellular matrix JF - DEVELOPMENT J2 - DEVELOPMENT VL - 143 PY - 2016 IS - 2 SP - 264 EP - 275 PG - 12 SN - 0950-1991 DO - 10.1242/dev.128132 UR - https://m2.mtmt.hu/api/publication/3002614 ID - 3002614 AB - The enteric nervous system (ENS) develops from neural crest cells that migrate along the intestine, differentiate into neurons and glia, and pattern into two plexuses within the gut wall. Inductive interactions between epithelium and mesenchyme regulate gut development, but the influence of these interactions on ENS development is unknown. Epithelial-mesenchymal recombinations were constructed using avian hindgut mesenchyme and non-intestinal epithelium from the bursa of Fabricius. These recombinations led to abnormally large and ectopically positioned ganglia. We hypothesized that sonic hedgehog (Shh), a secreted intestinal epithelial protein not expressed in the bursa, mediates this effect. Inhibition of Shh signaling, by addition of cyclopamine or a function-blocking antibody, resulted in large, ectopic ganglia adjacent to the epithelium. Shh overexpression, achieved in ovo using Shh-encoding retrovirus and in organ culture using recombinant protein, led to intestinal aganglionosis. Shh strongly induced the expression of versican and collagen type IX, whereas cyclopamine reduced expression of these chondroitin sulfate proteoglycans that are known to be inhibitory to neural crest cell migration. Shh also inhibited enteric neural crest-derived cell (ENCC) proliferation, promoted neuronal differentiation, and reduced expression of Gdnf, a key regulator of ENS formation. Ptc1 and Ptc2 were not expressed by ENCCs, and migration of isolated ENCCs was not inhibited by Shh protein. These results suggest that epithelial-derived Shh acts indirectly on the developing ENS by regulating the composition of the intestinal microenvironment. LA - English DB - MTMT ER - TY - JOUR AU - Hotta, R AU - Cheng, LS AU - Graham, HK AU - Pan, W AU - Nagy, Nándor AU - Belkind-Gerson, J AU - Goldstein, AM TI - Isogenic enteric neural progenitor cells can replace missing neurons and glia in mice with Hirschsprung disease. JF - NEUROGASTROENTEROLOGY AND MOTILITY J2 - NEUROGASTROENT MOTIL VL - 28 PY - 2016 IS - 4 SP - 498 EP - 512 PG - 15 SN - 1350-1925 DO - 10.1111/nmo.12744 UR - https://m2.mtmt.hu/api/publication/3002502 ID - 3002502 N1 - Department of Pediatric Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States Department of Surgery, University of California San Francisco, San Francisco, CA, United States Department of Pediatric Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China Department of Human Morphology and Developmental Biology, Faculty of Medicine, Semmelweis University, Budapest, Hungary Department of Pediatric Gastroenterology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States Pediatric Neurogastroenterology Program, Massachusetts General Hospital, United States Cited By :31 Export Date: 2 May 2022 CODEN: NMOTE Correspondence Address: Goldstein, A.M.; Department of Pediatric Surgery, Warren 1153, United States; email: agoldstein@partners.org AB - BACKGROUND: Transplanting autologous patient-derived enteric neuronal stem/progenitor cells (ENSCs) is an innovative approach to replacing missing enteric neurons in patients with Hirschsprung disease (HSCR). Using autologous cells eliminates immunologic and ethical concerns raised by other cell sources. However, whether postnatal aganglionic bowel is permissive for transplanted ENSCs and whether ENSCs from HSCR patients can be successfully isolated, cultured, and transplanted in vivo remains unknown. METHODS: ENSCs isolated from the ganglionic intestine of Ednrb-/- mice (HSCR-ENSCs) were characterized immunohistochemically and evaluated for their capacity to proliferate and differentiate in vitro. Fluorescently labeled ENSCs were co-cultured ex vivo with aganglionic Ednrb-/- colon. For in vivo transplantation, HSCR-ENSCs were labeled with lentivirus expressing green fluorescent protein (GFP) and implanted into aganglionic embryonic chick gut in ovo and postnatal aganglionic Ednrb-/- rectum in vivo. KEY RESULTS: HSCR-ENSCs maintain normal capacity self-renewal and neuronal differentiation. Moreover, the Ednrb-/- aganglionic environment is permissive to engraftment by wild-type ENSCs ex vivo and supports migratrion and neuroglial differentiation of these cells following transplantation in vivo. Lentiviral GFP-labeled HSCR-ENSCs populated embryonic chick hindgut and postnatal colon of Ednrb-/- HSCR, with cells populating the intermuscular layer and forming enteric neurons and glia. CONCLUSIONS & INFERENCES: ENSCs can be isolated and cultured from mice with HSCR, and transplanted into the aganglionic bowel of HSCR littermates to generate enteric neuronal networks. These results in an isogenic model establish the potential of using autologous-derived stem cells to treat HSCR and other intestinal neuropathies. LA - English DB - MTMT ER - TY - JOUR AU - Nagy, Nándor AU - Bódi, Ildikó AU - Oláh, Imre TI - Avian dendritic cells: phenotype and ontogeny in lymphoid organs JF - DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY J2 - DEV COMP IMMUNOL VL - 58 PY - 2016 SP - 47 EP - 59 PG - 13 SN - 0145-305X DO - 10.1016/j.dci.2015.12.020 UR - https://m2.mtmt.hu/api/publication/2995450 ID - 2995450 N1 - Cited By :17 Export Date: 5 February 2021 CODEN: DCIMD Correspondence Address: Nagy, N.; Semmelweis University, 85 Tuzolto str., Hungary; email: nagy.nandor@med.semmelweis-univ.hu AB - Dendritic cells (DC) are critically important accessory cells in the innate and adaptive immune systems. Avian DCs were originally identified in primary and secondary lymphoid organs by their typical morphology, displaying long cell processes with cytoplasmic granules. Several subtypes are known. Bursal secretory dendritic cells (BSDC) are elongated cells which express vimentin intermediate filaments, MHC II molecules, macrophage colony-stimulating factor 1 receptor (CSF1R), and produce 74.3+ secretory granules. Avian follicular dendritic cells (FDC) highly resemble BSDC, express the CD83, 74.3 and CSF1R molecules, and present antigen in germinal centers. Thymic dendritic cells (TDC), which express 74.3 and CD83, are concentrated in thymic medulla while interdigitating DC are found in T cell-rich areas of secondary lymphoid organs. Avian Langerhans cells are a specialized 74.3-/MHC II+ cell population found in stratified squamous epithelium and are capable of differentiating into 74.3+ migratory DCs. During organogenesis hematopoietic precursors of DC colonize the developing lymphoid organ primordia prior to immigration of lymphoid precursor cells. This review summarizes our current understanding of the ontogeny, cytoarchitecture, and immunophenotype of avian DC, and offers an antibody panel for the in vitro and in vivo identification of these heterogeneous cell types. LA - English DB - MTMT ER - TY - JOUR AU - Yonehara, K AU - Fiscella, M AU - Drinnenberg, A AU - Esposti, F AU - Trenholm, S AU - Krol, J AU - Franke, F AU - Scherf, BG AU - Kusnyerik, Ákos AU - Muller, J AU - Szabó, Arnold AU - Juttner, J AU - Cordoba, F AU - Reddy, AP AU - Németh, János Tibor AU - Nagy, Zoltán Zsolt AU - Munier, F AU - Hierlemann, A AU - Roska, Botond TI - Congenital Nystagmus Gene FRMD7 Is Necessary for Establishing a Neuronal Circuit Asymmetry for Direction Selectivity JF - NEURON J2 - NEURON VL - 89 PY - 2016 IS - 1 SP - 177 EP - 193 PG - 17 SN - 0896-6273 DO - 10.1016/j.neuron.2015.11.032 UR - https://m2.mtmt.hu/api/publication/2991176 ID - 2991176 AB - Neuronal circuit asymmetries are important components of brain circuits, but the molecular pathways leading to their establishment remain unknown. Here we found that the mutation of FRMD7, a gene that is defective in human congenital nystagmus, leads to the selective loss of the horizontal optokinetic reflex in mice, as it does in humans. This is accompanied by the selective loss of horizontal direction selectivity in retinal ganglion cells and the transition from asymmetric to symmetric inhibitory input to horizontal direction-selective ganglion cells. In wild-type retinas, we found FRMD7 specifically expressed in starburst amacrine cells, the interneuron type that provides asymmetric inhibition to direction-selective retinal ganglion cells. This work identifies FRMD7 as a key regulator in establishing a neuronal circuit asymmetry, and it suggests the involvement of a specific inhibitory neuron type in the pathophysiology of a neurological disease. LA - English DB - MTMT ER -