{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T12:26:32Z","timestamp":1780316792522,"version":"3.54.1"},"reference-count":52,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2020,12,18]],"date-time":"2020-12-18T00:00:00Z","timestamp":1608249600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Science Centre in Poland","award":["grant no. 2015\/17\/B\/NZ5\/02541"],"award-info":[{"award-number":["grant no. 2015\/17\/B\/NZ5\/02541"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Biosynthesis of melatonin by cholangiocytes is essential for maintaining the function of biliary epithelium. However, this cytoprotective mechanism appears to be impaired in primary biliary cholangitis (PBC). MiR-132 has emerged as a mediator of inflammation in chronic liver diseases. The effect of melatonin on oxidative stress and bile acid-induced apoptosis was also examined in cholangiocyes overexpressing miR506, as a PBC-like cellular model. In PBC patients the serum levels of melatonin were found increased in comparison to healthy controls. Whereas, in cholangiocytes within cirrhotic PBC livers the melatonin biosynthetic pathway was substantially suppressed even though the expressions of melatonin rate-limiting enzyme aralkylamine N-acetyltransferase (AANAT), and CK-19 (marker of cholangiocytes) were enhanced. In cholangiocytes exposed to mitochondrial oxidative stress melatonin decreased the expression of proapoptotic stimuli (PTEN, Bax, miR-34), which was accompanied by the inhibition of a pivotal mediator of inflammatory response Nf-\u03baB-p65 and the activation of antiapoptotic signaling (miR-132, Bcl2). Similarly, melatonin reduced bile acid-induced proapoptotic caspase 3 and Bim levels. In summary, the insufficient hepatic expression of melatonin in PBC patients may predispose cholangiocytes to oxidative stress-related damage. Melatonin, via epigenetic modulation, was able to suppress NF-\u03baB signaling activation and protect against biliary cells apoptotic signaling.<\/jats:p>","DOI":"10.3390\/ijms21249667","type":"journal-article","created":{"date-parts":[[2020,12,18]],"date-time":"2020-12-18T11:42:09Z","timestamp":1608291729000},"page":"9667","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Melatonin Protects Cholangiocytes from Oxidative Stress-Induced Proapoptotic and Proinflammatory Stimuli via miR-132 and miR-34"],"prefix":"10.3390","volume":"21","author":[{"given":"Ewa","family":"Ostrycharz","sequence":"first","affiliation":[{"name":"Department of Medical Biology, Pomeranian Medical University, 71-111 Szczecin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Urszula","family":"Wasik","sequence":"additional","affiliation":[{"name":"Department of Medical Biology, Pomeranian Medical University, 71-111 Szczecin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7513-8640","authenticated-orcid":false,"given":"Agnieszka","family":"Kempinska-Podhorodecka","sequence":"additional","affiliation":[{"name":"Department of Medical Biology, Pomeranian Medical University, 71-111 Szczecin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jesus M.","family":"Banales","sequence":"additional","affiliation":[{"name":"Department of Liver and Gastrointestinal Diseases, Biodonostia Health Research Institute-Donostia University Hospital-Ikerbasque, CIBERehd, University of the Basque Country (UPV\/EHU), 20014 San Sebastian, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piotr","family":"Milkiewicz","sequence":"additional","affiliation":[{"name":"Translational Medicine Group, Pomeranian Medical University, 71-210 Szczecin, Poland"},{"name":"Liver and Internal Medicine Unit, Medical University of Warsaw, 02-097 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2064-0545","authenticated-orcid":false,"given":"Malgorzata","family":"Milkiewicz","sequence":"additional","affiliation":[{"name":"Department of Medical Biology, Pomeranian Medical University, 71-111 Szczecin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,12,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1146\/annurev-pathol-020712-164014","article-title":"The immunobiology and pathophysiology of primary biliary cirrhosis","volume":"8","author":"Hirschfield","year":"2013","journal-title":"Annu. 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