{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T20:15:33Z","timestamp":1790972133667,"version":"4.1.0"},"reference-count":46,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","license":[{"start":{"date-parts":[[2018,2,21]],"date-time":"2018-02-21T00:00:00Z","timestamp":1519171200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"},{"start":{"date-parts":[[2018,2,21]],"date-time":"2018-02-21T00:00:00Z","timestamp":1519171200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2018,4]]},"abstract":"<jats:p>\n                    Primary biliary cholangitis (PBC) is a chronic cholestatic liver disease associated with autoimmune phenomena targeting intrahepatic bile duct cells (cholangiocytes). Although its etiopathogenesis remains obscure, development of antimitochondrial autoantibodies against pyruvate dehydrogenase complex E2 is a common feature. MicroRNA (miR) dysregulation occurs in liver and immune cells of PBC patients, but its functional relevance is largely unknown. We previously reported that miR\u2010506 is overexpressed in PBC cholangiocytes and directly targets both Cl\n                    <jats:sup>\u2013<\/jats:sup>\n                    \/\n\n                              \n                                 \n                              \n                            anion exchanger 2 and type III inositol 1,4,5\u2010trisphosphate receptor, leading to cholestasis. Here, the regulation of miR\u2010506 gene expression and its role in cholangiocyte pathophysiology and immune activation was studied. Several proinflammatory cytokines overexpressed in PBC livers (such as interleukin\u20108 [IL8], IL12, IL17, IL18, and tumor necrosis factor alpha) stimulated miR\u2010506 promoter activity in human cholangiocytes, as revealed by luciferase reporter assays. Experimental overexpression of miR\u2010506 in cholangiocytes dysregulated the cell proteomic profile (by mass spectrometry), affecting proteins involved in different biological processes including mitochondrial metabolism. In cholangiocytes, miR\u2010506 (1) induced dedifferentiation with down\u2010regulation of biliary and epithelial markers together with up\u2010regulation of mesenchymal, proinflammatory, and profibrotic markers; (2) impaired cell proliferation and adhesion; (3) increased oxidative and endoplasmic reticulum stress; (4) caused DNA damage; and (5) sensitized to caspase\u20103\u2010dependent apoptosis induced by cytotoxic bile acids. These events were also associated with impaired energy metabolism in mitochondria (proton leak and less adenosine triphosphate production) and pyruvate dehydrogenase complex E2 overexpression. Coculture of miR\u2010506 overexpressing cholangiocytes with PBC immunocytes induced activation and proliferation of PBC immunocytes.\n                    <jats:italic toggle=\"yes\">Conclusion<\/jats:italic>\n                    : Different proinflammatory cytokines enhance the expression of miR\u2010506 in biliary epithelial cells; miR\u2010506 induces PBC\u2010like features in cholangiocytes and promotes immune activation, representing a potential therapeutic target for PBC patients. (H\n                    <jats:sc>epatology<\/jats:sc>\n                    2018;67:1420\u20101440)\n                  <\/jats:p>","DOI":"10.1002\/hep.29533","type":"journal-article","created":{"date-parts":[[2017,9,18]],"date-time":"2017-09-18T10:44:08Z","timestamp":1505731448000},"page":"1420-1440","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":83,"title":["MicroRNA\u2010506 promotes primary biliary cholangitis\u2013like features in cholangiocytes and immune activation"],"prefix":"10.1097","volume":"67","author":[{"given":"Oihane","family":"Erice","sequence":"first","affiliation":[{"name":"Department of Liver and Gastrointestinal Diseases, Biodonostia Research Institute\u2013Donostia University Hospital,University of the Basque Country (UPV\/EHU),San Sebastian,Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Munoz\u2010Garrido","sequence":"additional","affiliation":[{"name":"Department of Liver and Gastrointestinal Diseases, Biodonostia Research Institute\u2013Donostia University Hospital,University of the Basque Country (UPV\/EHU),San Sebastian,Spain"},{"name":"National Institute for the Study of Liver and Gastrointestinal Diseases (CIBERehd),Carlos III National Institute of Health,Madrid,Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javier","family":"Vaquero","sequence":"additional","affiliation":[{"name":"Experimental Hepatology and Drug Targeting (HEVEFARM), Biomedical Research Institute of Salamanca (IBSAL),University of Salamanca,Salamanca,Spain"},{"name":"Sorbonne Universit\u00e9s, UPMC Universit\u00e9 Paris 06, INSERM, Saint\u2010Antoine Research Center, Paris, and Fondation 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Navarra,Pamplona,Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Saez","sequence":"additional","affiliation":[{"name":"Division of Hepatology,CIMA of the University of Navarra,Pamplona,Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alvaro","family":"Santos\u2010Laso","sequence":"additional","affiliation":[{"name":"Department of Liver and Gastrointestinal Diseases, Biodonostia Research Institute\u2013Donostia University Hospital,University of the Basque Country (UPV\/EHU),San Sebastian,Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ander","family":"Arbelaiz","sequence":"additional","affiliation":[{"name":"Department of Liver and Gastrointestinal Diseases, Biodonostia Research Institute\u2013Donostia University Hospital,University of the Basque Country (UPV\/EHU),San 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(IdiSNA),Pamplona,Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ver\u00f3nica","family":"Torrano","sequence":"additional","affiliation":[{"name":"CIC bioGUNE, Bizkaia Technology Park,Derio,Bizkaia,Spain"},{"name":"CIBERONC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arkaitz","family":"Carracedo","sequence":"additional","affiliation":[{"name":"IKERBASQUE, Basque Foundation for Science,Bilbao,Spain"},{"name":"CIC bioGUNE, Bizkaia Technology Park,Derio,Bizkaia,Spain"},{"name":"CIBERONC"},{"name":"Biochemistry and Molecular Biology Department,University of the Basque Country (UPV\/EHU),Bilbao,Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meenakshisundaram","family":"Ananthanarayanan","sequence":"additional","affiliation":[{"name":"Liver Center,Yale University School of Medicine,New 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