{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T18:13:23Z","timestamp":1792260803196,"version":"4.4.0"},"reference-count":38,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2023,4,7]],"date-time":"2023-04-07T00:00:00Z","timestamp":1680825600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["FEBS Open Bio"],"published-print":{"date-parts":[[2023,5]]},"abstract":"<jats:p>Ductular reaction (DR) is usually observed in biliary disorders or various liver disorders, including nonalcoholic fatty liver disease. Few studies have focused on interrupting the DR process in the cholestatic environment. Here, we investigated the impact of reversine on DR in rats that had undergone bile duct ligation (BDL). Cholestatic injury was induced in rats 2\u2009weeks following BDL. DR was assessed with biliary markers by immunohistochemistry. Biliary epithelial cells (BECs) were isolated for the analysis of proliferation and biliary factor gene expression. The effects of reversine on DR and fibrosis were analyzed <jats:italic>in vivo<\/jats:italic> via intraperitoneal injection in rats for 2\u2009weeks. Chemically\u2010induced BEC formation was used to investigate the biliary markers affected by reversine <jats:italic>in vitro<\/jats:italic>. DR with increased BEC expansion was identified in cholestatic liver injury, as indicated by CK7, CK19, and EpCAM expression around the portal vein in BDL rats. BDL\u2010induced DR cells showed the increased expression of genes regulating cell proliferation (<jats:italic>Ki67<\/jats:italic>, <jats:italic>Foxm1<\/jats:italic>, and <jats:italic>Pcna<\/jats:italic>) and biliary markers (<jats:italic>Krt7<\/jats:italic>, <jats:italic>Krt19<\/jats:italic>, <jats:italic>Epcam<\/jats:italic>, <jats:italic>Sox9<\/jats:italic>, <jats:italic>Cftr<\/jats:italic>, and <jats:italic>Asbt<\/jats:italic>). Reversine attenuated cholestatic fibrosis and DR in rats. Reversine affected chemically\u2010induced BEC formation, with the decreased expression of biliary <jats:italic>Krt7<\/jats:italic>, <jats:italic>Cftr<\/jats:italic>, and <jats:italic>Ggt1<\/jats:italic> genes <jats:italic>in vitro<\/jats:italic>. BDL\u2010induced Notch activation was attenuated upon reversine treatment <jats:italic>in vivo<\/jats:italic>, in part via the Notch\/Sox9 pathway. In conclusion, reversine attenuated cholestatic ductular reaction and fibrosis in rats and reduced the bile duct formation associated with Dlk1\/Notch\/Sox9 signaling. Reversine may be regarded as a potential drug for cholangiopathies for preventing a ductular reaction.<\/jats:p>","DOI":"10.1002\/2211-5463.13596","type":"journal-article","created":{"date-parts":[[2023,3,16]],"date-time":"2023-03-16T14:44:46Z","timestamp":1678977886000},"page":"898-911","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Reversine attenuates cholestatic ductular reaction in rats"],"prefix":"10.1002","volume":"13","author":[{"given":"Di","family":"Huang","sequence":"first","affiliation":[{"name":"Department of Surgery Guangzhou First People's Hospital  Guangzhou China"},{"name":"Guangzhou Digestive Disease Center Guangzhou First People's Hospital  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lijuan","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Emergency The Second Affiliated Hospital of Guangzhou University of Chinese Medicine  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