{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T18:13:27Z","timestamp":1792260807827,"version":"4.4.0"},"reference-count":29,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","license":[{"start":{"date-parts":[[2019,4,11]],"date-time":"2019-04-11T00:00:00Z","timestamp":1554940800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2019,6]]},"abstract":"<jats:p>In patients with biliary atresia (BA), the extent of intrahepatic biliary fibrosis negatively correlates with successful surgical bypass of the congenital cholangiopathy as well as subsequent transplant\u2010free survival. We recently linked the expansion of a population of <jats:italic toggle=\"yes\">prominin\u20101<\/jats:italic> (<jats:italic toggle=\"yes\">Prom1<\/jats:italic>)\u2010expressing hepatic progenitor cells to biliary fibrogenesis. Herein, we hypothesized that <jats:italic toggle=\"yes\">Prom1<\/jats:italic>\u2010expressing progenitor cells play a role in BA\u2010associated fibrosis. Rhesus rotavirus (RRV)\u2010mediated experimental BA was induced in newborn mice homozygous for the transgene <jats:italic toggle=\"yes\">Prom1cre\u2010ert2\u2010nlacz\n                           <\/jats:italic>, which was knocked in to the <jats:italic toggle=\"yes\">Prom1<\/jats:italic> gene locus, thus creating functional <jats:italic toggle=\"yes\">Prom1<\/jats:italic> knockout (KO) mice, and their wildtype (WT) littermates. Clinical data and tissue samples from BA infants from the Childhood Liver Disease Research Consortium were analyzed. Extrahepatic biliary obliteration was present in both WT and KO mice; there was no difference in serum total bilirubin (TBili) levels. The intrahepatic periportal expansion of the PROM1<jats:sup>pos<\/jats:sup> cell population, typically observed in RRV\u2010induced BA, was absent in KO mice. RRV\u2010treated KO mice demonstrated significantly fewer cytokeratin\u201019 (CK19)\u2010positive ductular reactions (<jats:italic toggle=\"yes\">P<\/jats:italic> = 0.0004) and significantly less periportal collagen deposition (<jats:italic toggle=\"yes\">P <\/jats:italic>= 0.0001) compared with WT. RRV\u2010treated KO mice expressed significantly less <jats:italic toggle=\"yes\">integrin\u2010\u03b26<\/jats:italic>, which encodes a key biliary\u2010specific subunit of a transforming growth factor (TGF) \u03b2 activator (<jats:italic toggle=\"yes\">P<\/jats:italic> = 0.0004). Infants with successful biliary drainage (Tbili \u22641.5 mg\/dL within 3 months postoperatively), which is highly predictive of increased transplant\u2010free survival, expressed significantly less hepatic <jats:italic toggle=\"yes\">PROM1<\/jats:italic>, <jats:italic toggle=\"yes\">CK19<\/jats:italic>, and <jats:italic toggle=\"yes\">COLLAGEN\u20101\u03b1<\/jats:italic> compared with those with TBili &gt;1.5 (<jats:italic toggle=\"yes\">P <\/jats:italic>&lt; 0.05). <jats:italic toggle=\"yes\">Conclusion:<\/jats:italic>\n                           <jats:italic toggle=\"yes\">Prom1<\/jats:italic> plays an important role in biliary fibrogenesis, in part through integrin\u2010mediated TGF pathway activation.<\/jats:p>","DOI":"10.1002\/hep.30550","type":"journal-article","created":{"date-parts":[[2019,2,6]],"date-time":"2019-02-06T01:43:22Z","timestamp":1549417402000},"page":"2586-2597","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":21,"title":["Prominin\u20101 Promotes Biliary Fibrosis Associated With Biliary Atresia"],"prefix":"10.1097","volume":"69","author":[{"given":"Jessica A.","family":"Zagory","sequence":"first","affiliation":[{"name":"Department of Surgery,Children\u2019s Hospital Los Angeles,Los Angeles,CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Fenlon","sequence":"additional","affiliation":[{"name":"Department of Surgery,Children\u2019s Hospital Los Angeles,Los Angeles,CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Dietz","sequence":"additional","affiliation":[{"name":"Department of Surgery,Children\u2019s Hospital Los Angeles,Los Angeles,CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Menghan","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Surgery,Children\u2019s Hospital Los Angeles,Los Angeles,CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie V.","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Department of Surgery,Children\u2019s Hospital Los Angeles,Los Angeles,CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pavin","family":"Trinh","sequence":"additional","affiliation":[{"name":"Department of Surgery,Children\u2019s Hospital Los Angeles,Los Angeles,CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maeva","family":"Adoumie","sequence":"additional","affiliation":[{"name":"Department of Surgery,Children\u2019s Hospital Los Angeles,Los Angeles,CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2346-5949","authenticated-orcid":false,"given":"Alex","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Surgery,Children\u2019s Hospital Los Angeles,Los Angeles,CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiabo","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Surgery,Children\u2019s Hospital Los Angeles,Los Angeles,CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elaa","family":"Mahdi","sequence":"additional","affiliation":[{"name":"Department of Surgery,Children\u2019s Hospital Los Angeles,Los Angeles,CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alison","family":"Glazier","sequence":"additional","affiliation":[{"name":"Department of Surgery,Children\u2019s Hospital Los Angeles,Los Angeles,CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Malkoff","sequence":"additional","affiliation":[{"name":"Department of Surgery,Children\u2019s Hospital Los Angeles,Los Angeles,CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nirmala","family":"Mavila","sequence":"additional","affiliation":[{"name":"Department of Surgery,Children\u2019s Hospital Los Angeles,Los Angeles,CA"},{"name":"Department of Gastroenterology, Cedars\u2010Sinai Medical Center,Los Angeles,CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kasper S.","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Surgery,Children\u2019s Hospital Los Angeles,Los Angeles,CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"in conjunction with the Childhood Liver Disease Research Network","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2019,4,11]]},"reference":[{"key":"hep30550-bib-0001-20250212","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1146\/annurev-med-042909-093734","article-title":"Biliary atresia: will blocking inflammation tame the disease?","volume":"62","year":"2011","journal-title":"Annu Rev Med"},{"key":"hep30550-bib-0002-20250212","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1053\/j.sempedsurg.2012.05.003","article-title":"Biliary atresia: cellular dynamics and immune dysregulation","volume":"21","year":"2012","journal-title":"Semin Pediatr Surg"},{"key":"hep30550-bib-0003-20250212","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1111\/petr.12040","article-title":"Current options for management of biliary atresia","volume":"17","year":"2013","journal-title":"Pediatr 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workshop","volume":"46","year":"2007","journal-title":"Hepatology"},{"key":"hep30550-bib-0008-20250212","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1097\/SLA.0b013e3182300950","article-title":"The anatomic pattern of biliary atresia identified at time of Kasai hepatoportoenterostomy and early postoperative clearance of jaundice are significant predictors of transplant\u2010free survival","volume":"254","year":"2011","journal-title":"Ann Surg"},{"key":"hep30550-bib-0009-20250212","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1002\/hep.27203","article-title":"Expansion of prominin\u20101\u2010expressing cells in association with fibrosis of biliary atresia","volume":"60","year":"2014","journal-title":"Hepatology"},{"key":"hep30550-bib-0010-20250212","doi-asserted-by":"crossref","first-page":"e50401","DOI":"10.1371\/journal.pone.0050401","article-title":"Fibroblast growth factor receptor\u2010mediated activation of AKT\u2010beta\u2010catenin\u2010CBP pathway regulates survival and proliferation of murine hepatoblasts and hepatic tumor initiating stem cells","volume":"7","year":"2012","journal-title":"PLoS One"},{"key":"hep30550-bib-0011-20250212","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1038\/nature07589","article-title":"Prominin 1 marks intestinal stem cells that are susceptible to neoplastic transformation","volume":"457","year":"2009","journal-title":"Nature"},{"key":"hep30550-bib-0012-20250212","doi-asserted-by":"crossref","first-page":"1132","DOI":"10.1016\/j.cell.2016.07.045","article-title":"Multi\u2010organ mapping of cancer risk","volume":"166","year":"2016","journal-title":"Cell"},{"key":"hep30550-bib-0013-20250212","article-title":"Heterogeneity and stochastic growth regulation of biliary epithelial cells dictate dynamic epithelial tissue remodeling","volume":"5","year":"2016","journal-title":"Elife"},{"key":"hep30550-bib-0014-20250212","doi-asserted-by":"crossref","first-page":"1266","DOI":"10.1016\/j.surg.2016.09.043","article-title":"Hepatic Prominin\u20101 expression is associated with biliary fibrosis","volume":"161","year":"2017","journal-title":"Surgery"},{"key":"hep30550-bib-0015-20250212","doi-asserted-by":"crossref","first-page":"G425","DOI":"10.1152\/ajpgi.00050.2011","article-title":"Role of integrins in fibrosing liver diseases","volume":"301","year":"2011","journal-title":"Am J Physiol Gastrointest Liver Physiol"},{"key":"hep30550-bib-0016-20250212","doi-asserted-by":"crossref","first-page":"660","DOI":"10.1053\/j.gastro.2008.04.009","article-title":"Inhibition of integrin alphavbeta6 on cholangiocytes blocks transforming growth factor\u2010beta activation and retards biliary fibrosis 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Pediatr"},{"key":"hep30550-bib-0026-20250212","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1016\/j.jss.2012.05.082","article-title":"Rotavirus infection of human cholangiocytes parallels the murine model of biliary atresia","volume":"177","year":"2012","journal-title":"J Surg Res"},{"key":"hep30550-bib-0027-20250212","doi-asserted-by":"crossref","first-page":"e69069","DOI":"10.1371\/journal.pone.0069069","article-title":"Rotavirus replication in the cholangiocyte mediates the temporal dependence of murine biliary atresia","volume":"8","year":"2013","journal-title":"PLoS One"},{"key":"hep30550-bib-0028-20250212","doi-asserted-by":"crossref","first-page":"1404","DOI":"10.1002\/hep.21849","article-title":"Role of alphavbeta6 integrin in acute biliary fibrosis","volume":"46","year":"2007","journal-title":"Hepatology"},{"key":"hep30550-bib-0029-20250212","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1002\/hep.28274","article-title":"Integrin alphavbeta6 critically 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History"}},{"value":"2019-01-29","name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}}]}}