{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T18:13:22Z","timestamp":1792260802669,"version":"4.4.0"},"reference-count":43,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2015,8,3]],"date-time":"2015-08-03T00:00:00Z","timestamp":1438560000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"German Research Organization","award":["STR 1095\/2-1"],"award-info":[{"award-number":["STR 1095\/2-1"]}]},{"name":"German Research Organization","award":["SFB TRR57"],"award-info":[{"award-number":["SFB TRR57"]}]},{"name":"Interdisciplinary Center for Clinical Research (IZKF), Faculty of Medicine RWTH University Aachen"}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology"],"published-print":{"date-parts":[[2015,11]]},"abstract":"Abstract<\/jats:title>Keratins (K) are cytoprotective proteins and keratin mutations predispose to the development of multiple human diseases. K19<\/jats:styled-content> represents the most widely used marker of biliary and hepatic progenitor cells as well as a marker of ductular reaction that constitutes the basic regenerative response to chronic liver injury. In the present study, we investigated the role of K19<\/jats:styled-content> in biliary and hepatic progenitor cells and its importance for ductular reaction. K19<\/jats:styled-content> wild\u2010type (WT<\/jats:styled-content>) and knockout (KO<\/jats:styled-content>) mice were fed: (a) 3,5\u2010diethoxycarbonyl\u20101,4\u2010dihydrocollidine (DDC<\/jats:styled-content>); (b) cholic acid (CA<\/jats:styled-content>); (c) a choline\u2010deficient, ethionine\u2010supplemented (CDE<\/jats:styled-content>) diet; or (d) were subjected to common bile duct ligation (CBDL<\/jats:styled-content>). The bile composition, liver damage, bile duct proliferation, oval cell content and biliary fibrosis were analysed. In untreated animals, loss of K19<\/jats:styled-content> led to redistribution of the K network in biliary epithelial cells (BECs<\/jats:styled-content>) but to no obvious biliary phenotype. After DDC<\/jats:styled-content> feeding, K19 KO<\/jats:styled-content> mice exhibited (compared to WTs<\/jats:styled-content>): (a) increased cholestasis; (b) less pronounced ductular reaction with reduced ductular proliferation and fewer oval cells; (c) impaired Notch 2 signalling in BECs<\/jats:styled-content>; (d) lower biliary fibrosis score and biliary bicarbonate concentration. An attenuated oval cell proliferation in K19 KOs<\/jats:styled-content> was also found after feeding with the CDE<\/jats:styled-content> diet. K19 KOs<\/jats:styled-content> subjected to CBDL<\/jats:styled-content> displayed lower BEC<\/jats:styled-content> proliferation, oval cell content and less prominent Notch 2 signal. K19<\/jats:styled-content> deficiency did not change the extent of CA<\/jats:styled-content>\u2010 or CBDL<\/jats:styled-content>\u2010induced liver injury and fibrosis. Our results demonstrate that K19<\/jats:styled-content> plays an important role in the ductular reaction and might be of importance in multiple chronic liver disorders that frequently display a ductular reaction. Copyright \u00a9 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.<\/jats:p>","DOI":"10.1002\/path.4580","type":"journal-article","created":{"date-parts":[[2015,6,25]],"date-time":"2015-06-25T02:23:04Z","timestamp":1435198984000},"page":"343-354","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Loss of keratin 19 favours the development of cholestatic liver disease through decreased ductular reaction"],"prefix":"10.1002","volume":"237","author":[{"given":"Yu","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Internal Medicine III and IZKF RWTH Aachen Germany"},{"name":"Department of Internal Medicine I University Medical Centre Ulm Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nurdan","family":"Guldiken","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine III and IZKF RWTH Aachen Germany"},{"name":"Department of Internal Medicine I University Medical Centre Ulm 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