{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T11:32:22Z","timestamp":1790422342190,"version":"4.1.0"},"reference-count":42,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"12","license":[{"start":{"date-parts":[[2021,8,25]],"date-time":"2021-08-25T00:00:00Z","timestamp":1629849600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatol Commun"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:p>We previously identified an up\u2010regulation of specific Wnt proteins in the cholangiocyte compartment during cholestatic liver injury and found that mice lacking Wnt secretion from hepatocytes and cholangiocytes showed fewer proliferating cholangiocytes and high mortality in response to a 3,5\u2010diethoxycarbonyl\u20101,4\u2010dihydrocollidine (DDC) diet, a murine model of primary sclerosing cholangitis. <jats:italic toggle=\"yes\">In vitro<\/jats:italic> studies demonstrated that Wnt7b, one of the Wnts up\u2010regulated during cholestasis, induces proliferation of cholangiocytes in an autocrine manner and increases secretion of proinflammatory cytokines. We hypothesized that loss of Wnt7b may exacerbate some of the complications of cholangiopathies by decreasing the ability of bile ducts to induce repair. Wnt7b\u2010flox mice were bred with Krt19\u2010cre mice to deplete Wnt7b expression in only cholangiocytes (CC) or with albumin\u2010Cre mice to delete Wnt7b expression in both hepatocytes and cholangiocytes (HC + CC). These mice were placed on a DDC diet for 1\u00a0month then killed for evaluation. Contrary to our expectations, we found that mice lacking Wnt7b from CC and HC + CC compartments had improved biliary injury, decreased cellular senescence, and lesser bile acid accumulation after DDC exposure compared to controls, along with decreased expression of inflammatory cytokines. Although Wnt7b knockout (KO) resulted in fewer proliferating cholangiocytes, CC and HC + CC KO mice on a DDC diet also had more hepatocytes expressing cholangiocyte markers compared to wild\u2010type mice on a DDC diet, indicating that Wnt7b suppression promotes hepatocyte reprogramming. <jats:italic toggle=\"yes\">Conclusion:<\/jats:italic> Wnt7b induces a proproliferative proinflammatory program in cholangiocytes, and its loss is compensated for by conversion of hepatocytes to a biliary phenotype during cholestatic injury.<\/jats:p>","DOI":"10.1002\/hep4.1784","type":"journal-article","created":{"date-parts":[[2021,8,26]],"date-time":"2021-08-26T05:36:11Z","timestamp":1629956171000},"page":"2019-2034","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":18,"title":["WNT7B Regulates Cholangiocyte Proliferation and Function During Murine Cholestasis"],"prefix":"10.1097","volume":"5","author":[{"given":"Karis","family":"Kosar","sequence":"first","affiliation":[{"name":"Department of Pathology,University of Pittsburgh,Pittsburgh,PA,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pamela","family":"Cornuet","sequence":"additional","affiliation":[{"name":"Department of Pathology,University of Pittsburgh,Pittsburgh,PA,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sucha","family":"Singh","sequence":"additional","affiliation":[{"name":"Department of Pathology,University of Pittsburgh,Pittsburgh,PA,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Pathology,University of Pittsburgh,Pittsburgh,PA,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pathology,University of 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