{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T05:29:13Z","timestamp":1783488553436,"version":"3.55.0"},"reference-count":29,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2022,3,16]],"date-time":"2022-03-16T00:00:00Z","timestamp":1647388800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"US-Israel BSF","award":["grant #2017-212"],"award-info":[{"award-number":["grant #2017-212"]}]},{"name":"Fred and Suzan Biesecker Pediatric Liver Center grants"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Bile duct integrity is essential for the maintenance of the structure and function of the biliary tree. We previously showed that cholangiocyte injury in a toxic model of biliary atresia leads to increased monolayer permeability. Increased epithelial permeability was also shown in other cholangiopathies. We hypothesized that after initial cholangiocyte injury, leakage of bile acids into the duct submucosa propagates cholangiocyte damage and fibrosis. We thus aimed to determine the impact of bile acid exposure on cholangiocytes and the potential therapeutic effect of a non-toxic bile acid.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Materials and methods<\/jats:title>\n                    <jats:p>Extrahepatic bile duct explants were isolated from adult and neonatal BALB\/c mice. Explants were cultured with or without glycochenodeoxycholic acid and ursodeoxycholic acid. They were then fixed and stained.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Explants treated with glycochenodeoxycholic acid demonstrated cholangiocyte injury with monolayer disruption and partial lumen obstruction compared to control ducts. Masson\u2019s trichrome stains revealed increased collagen fibers. Myofibroblast marker \u03b1-SMA stains were significantly elevated in the periductal region. The addition of ursodeoxycholic acid resulted in decreased cholangiocyte injury and reduced fibrosis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Bile acid leakage into the submucosa after initial cholangiocyte injury may serve as a possible mechanism of disease propagation and progressive fibrosis in cholangiopathies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0265418","type":"journal-article","created":{"date-parts":[[2022,3,16]],"date-time":"2022-03-16T13:34:19Z","timestamp":1647437659000},"page":"e0265418","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":13,"title":["Periductal bile acid exposure causes cholangiocyte injury and fibrosis"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6308-0181","authenticated-orcid":true,"given":"Miri","family":"Dotan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophia","family":"Fried","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adi","family":"Har-Zahav","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raanan","family":"Shamir","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6988-4102","authenticated-orcid":true,"given":"Rebecca G.","family":"Wells","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0410-175X","authenticated-orcid":true,"given":"Orith","family":"Waisbourd-Zinman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2022,3,16]]},"reference":[{"key":"pone.0265418.ref001","doi-asserted-by":"crossref","first-page":"2647","DOI":"10.1001\/archinte.159.22.2647","article-title":"The continuing importance of bile acids in liver and intestinal disease","volume":"159","author":"AF Hofmann","year":"1999","journal-title":"Arch Intern Med"},{"key":"pone.0265418.ref002","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/bs.apha.2015.04.003","article-title":"Bile acid metabolism and signaling in cholestasis, inflammation, and cancer","volume":"74","author":"T Li","year":"2015","journal-title":"Adv 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