{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T11:31:27Z","timestamp":1774438287028,"version":"3.50.1"},"reference-count":56,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2022,3,18]],"date-time":"2022-03-18T00:00:00Z","timestamp":1647561600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004281","name":"National Science Center","doi-asserted-by":"publisher","award":["2017\/25\/B\/NZ5\/00819"],"award-info":[{"award-number":["2017\/25\/B\/NZ5\/00819"]}],"id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Primary biliary cholangitis (PBC) is a rare chronic cholestatic and immune-mediated liver disease of unknown aetiology that targets intrahepatic bile duct cells (cholangiocytes) and primarily affects postmenopausal women, when their estrogen levels sharply decrease. An impaired cholangiocyte response to estrogen characterizes the terminal stage of the disease, as this is when an inefficiency of cholangiocyte proliferation, in balancing the loss of intrahepatic bile ducts, is observed. Here, we report that the estrogen precursor dehydroepiandrosterone (DHEA) and its sulfate metabolites, DHEA-S and 17 \u03b2-estradiol, enhance the proliferation of cholangiocytes and hepatocytes in vitro. Flow cytometry analysis showed that DHEA and DHEA-S decreased glyco-chenodeoxycholic acid (GCDC)-driven apoptosis in cholangiocytes. Cell viability assay (MTT) indicated that ER-\u03b1, -\u03b2, and the G-protein-coupled estrogen receptor, are involved in the protection of DHEA against oxidative stress in cholangiocytes. Finally, immunoblot analysis showed an elevated level of steroid sulfatase and a reduced level of sulfotransferase 1E1 enzymes, involved in the desulfation\/sulfation process of estrogens in cirrhotic PBC, and primary sclerosis cholangitis (PSC) liver tissues, another type of chronic cholestatic and immune-mediated liver disease. Taken together, these results suggest that DHEA can prevent the deleterious effects of certain potentially toxic bile acids and reactive oxygen species, delaying the onset of liver disease.<\/jats:p>","DOI":"10.3390\/cells11061038","type":"journal-article","created":{"date-parts":[[2022,3,20]],"date-time":"2022-03-20T21:25:00Z","timestamp":1647811500000},"page":"1038","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["DHEA Protects Human Cholangiocytes and Hepatocytes against Apoptosis and Oxidative Stress"],"prefix":"10.3390","volume":"11","author":[{"given":"Ewa","family":"Kilanczyk","sequence":"first","affiliation":[{"name":"Department of Medical Biology, Pomeranian Medical University, 70-204 Szczecin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dagmara","family":"Ruminkiewicz","sequence":"additional","affiliation":[{"name":"Department of Medical Biology, Pomeranian Medical University, 70-204 Szczecin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jesus M.","family":"Banales","sequence":"additional","affiliation":[{"name":"Department of Liver and Gastrointestinal Diseases, Biodonostia Health Research Institute, Donostia University Hospital, University of the Basque Country (UPV\/EHU), CIBERehd, Ikerbasque, 20014 San Sebastian, Spain"},{"name":"Department of Biochemistry and Genetics, School of Science, University of Navarra, 31009 Pamplona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Piotr","family":"Milkiewicz","sequence":"additional","affiliation":[{"name":"Translational Medicine Group, Pomeranian Medical University, 70-204 Szczecin, Poland"},{"name":"Liver and Internal Medicine Unit, Medical University of Warsaw, 02-097 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2064-0545","authenticated-orcid":false,"given":"Ma\u0142gorzata","family":"Milkiewicz","sequence":"additional","affiliation":[{"name":"Department of Medical Biology, Pomeranian Medical University, 70-204 Szczecin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1016\/S0168-8278(00)80377-3","article-title":"Regulation and deregulation of cholangiocyte proliferation","volume":"33","author":"Alvaro","year":"2000","journal-title":"J. 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