{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T15:45:44Z","timestamp":1764603944311,"version":"3.40.5"},"reference-count":36,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2023,3,26]],"date-time":"2023-03-26T00:00:00Z","timestamp":1679788800000},"content-version":"vor","delay-in-days":84,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81870431","82030021","82072641"],"award-info":[{"award-number":["81870431","82030021","82072641"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Digest Diseases"],"published-print":{"date-parts":[[2023,1]]},"abstract":"<jats:sec><jats:title>Objectives<\/jats:title><jats:p>Previous studies have demonstrated the pivotal role of transforming\u00a0growth factor (TGF)\u2010\u03b2 signaling in activating hepatic stellate cells during liver fibrosis. In this study we aimed to demonstrate the effects and underlying mechanism of TGF\u2010\u03b2 signaling in hepatocytes on hepatic fibrogenesis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Hepatocyte\u2010specific <jats:italic>Tgfbr2<\/jats:italic>\u2010knockout (<jats:italic>Tgfbr2<\/jats:italic><jats:sup>HKO<\/jats:sup>) mice were generated by AAV8\u2010TBG\u2010Cre injection via the tail vein of <jats:italic>Tgfbr2<\/jats:italic><jats:sup>f\/f<\/jats:sup> mice. CCl<jats:sub>4<\/jats:sub> was injected intraperitoneally twice a week for 4\u2009weeks to establish the fibrotic mouse model. The expression of the fibrogenesis markers was evaluated by immunohistochemistry, western blot, and real\u2010time polymerase chain reaction (PCR). RNA\u2010seq analysis was used to detect the transcriptional profiles of primary hepatocytes isolated from <jats:italic>Tgfbr2<\/jats:italic><jats:sup>HKO<\/jats:sup> mice and control mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The expression of T\u03b2R2 (<jats:italic>Tgfbr2<\/jats:italic>) was markedly upregulated in hepatocytes of the fibrotic liver. <jats:italic>Tgfbr2<\/jats:italic> depletion in hepatocytes decreased the expressions of profibrogenic markers (<jats:italic>Col1a1<\/jats:italic> and <jats:italic>Acta2<\/jats:italic>) in the CCl<jats:sub>4<\/jats:sub>\u2010treated fibrotic liver. RNA\u2010seq analysis revealed that <jats:italic>Tgfbr2<\/jats:italic> deletion in hepatocytes significantly reduced the inflammatory response and suppressed epithelial\u2013mesenchymal transition of hepatocytes accompanied by upregulation of the metabolic pathways during liver fibrosis. Moreover, the expressions of hepatocyte nuclear factors (HNFs), including <jats:italic>Hnf4\u03b1<\/jats:italic>, <jats:italic>Foxa1<\/jats:italic>, <jats:italic>Foxa2<\/jats:italic>, and <jats:italic>Foxa3<\/jats:italic>, which are important for maintaining liver metabolism and homeostasis, were decreased in fibrotic livers and significantly increased after <jats:italic>Tgfbr2<\/jats:italic> blockade.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Blocking the TGF\u2010\u03b2 signaling pathway in hepatocytes reduces hepatic fibrosis and improves hepatic function in fibrotic livers.<\/jats:p><\/jats:sec>","DOI":"10.1111\/1751-2980.13161","type":"journal-article","created":{"date-parts":[[2023,2,15]],"date-time":"2023-02-15T14:34:48Z","timestamp":1676471688000},"page":"39-50","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Depletion of <i>Tgfbr2<\/i> in hepatocytes alleviates liver fibrosis and restores hepatic function in fibrotic mice"],"prefix":"10.1111","volume":"24","author":[{"given":"Shu Qing","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Gastroenterology, Changzheng Hospital Naval Medical University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xing","family":"Deng","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Changzheng Hospital Naval Medical University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chang Peng","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Changzheng Hospital Naval Medical University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ya Lu","family":"Cui","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Changzheng Hospital Naval Medical University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7137-112X","authenticated-orcid":false,"given":"Wei Fen","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Changzheng Hospital Naval Medical University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Changzheng Hospital Naval Medical University  Shanghai 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