{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T16:19:49Z","timestamp":1791821989938,"version":"4.3.4"},"reference-count":43,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2025,6,27]],"date-time":"2025-06-27T00:00:00Z","timestamp":1750982400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2025,6,27]],"date-time":"2025-06-27T00:00:00Z","timestamp":1750982400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100007219","name":"Natural Science Foundation of Shanghai Municipality","doi-asserted-by":"publisher","award":["14ZR1408900"],"award-info":[{"award-number":["14ZR1408900"]}],"id":[{"id":"10.13039\/100007219","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81472772"],"award-info":[{"award-number":["81472772"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100018537","name":"National Science and Technology Major Project","doi-asserted-by":"publisher","award":["2018ZX10302207"],"award-info":[{"award-number":["2018ZX10302207"]}],"id":[{"id":"10.13039\/501100018537","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and Aims<\/jats:title>\n                    <jats:p>Liver fibrosis, a progressive condition driven by chronic liver injury and excessive scar tissue formation, can lead to cirrhosis, a life\u2010threatening disease. Activation of hepatic stellate cells (HSCs) is central to fibrosis progression, yet current therapies fail to halt or reverse this process. This study evaluated a combination therapy targeting HSCs to ameliorate fibrosis and promote liver repair.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      A small molecule cocktail, SBCH (SB431542, a TGF\u2010\u03b2 inhibitor, and CHIR99021, a GSK\u20103 inhibitor), was tested in three fibrosis models: CCl\n                      <jats:sub>4<\/jats:sub>\n                      \u2010induced, bile duct ligation (BDL) and non\u2010alcoholic steatohepatitis (NASH) with diethylnitrosamine (DEN). Therapeutic effects were assessed using phenotypic analyses, in\u00a0vivo tracing and single\u2010cell RNA sequencing to uncover mechanisms.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>SBCH significantly reduced fibrosis in all models by inhibiting HSC activation and fibrogenic activity. The suppression of PI3K\/Akt pathway and EMT cascade contribute to the fibrosis\u2010ameliorating effect of SBCH treatment. Furthermore, in\u00a0vivo tracing and single\u2010cell RNA sequencing revealed that SBCH induced the conversion of activated HSCs into hepatocyte\u2010like cells (ciHeps), which integrated into liver tissue, repaired liver damage and restored liver integrity and function.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>SBCH mitigates liver fibrosis through multifaceted mechanisms, including the inhibition of HSC activation, suppression of fibrogenic activity and regulation of key signalling pathways such as PI3K\/Akt and EMT. In addition, SBCH induces the trans\u2010differentiation of activated HSCs into hepatocyte\u2010like cells (ciHeps), effectively reducing pathogenic HSCs while increasing functional ciHeps. This dual\u2010target approach not only facilitates liver tissue repair but also restores liver function, offering a promising therapeutic strategy for liver fibrosis and cirrhosis, with potential applications in conditions arising from various aetiologies of liver injury.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/liv.70187","type":"journal-article","created":{"date-parts":[[2025,6,27]],"date-time":"2025-06-27T05:27:19Z","timestamp":1751002039000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Amelioration of Liver Fibrosis via In\u00a0Situ Hepatic Stellate Cell Conversion Through Co\u2010Inhibition of\n                    <scp>TGF<\/scp>\n                    \u2010\u03b2 and\n                    <scp>GSK<\/scp>\n                    \u20103 Signalling"],"prefix":"10.1111","volume":"45","author":[{"given":"Xiang\u2010Jie","family":"Zhu","sequence":"first","affiliation":[{"name":"Institute of Metabolism &amp; Integrative Biology Fudan University  Shanghai China"},{"name":"National Center for Liver Cancer  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi","family":"Zhong","sequence":"additional","affiliation":[{"name":"National Center for Liver Cancer  Shanghai China"},{"name":"Department of Oncology, Fudan University Shanghai Cancer Center, Shanghai Medical College Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiang\u2010Chuan","family":"Du","sequence":"additional","affiliation":[{"name":"National Center for Liver Cancer  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiu\u2010Yu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Institute of Metabolism &amp; Integrative Biology Fudan University  Shanghai China"},{"name":"National Center for Liver Cancer  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xu","family":"Zhang","sequence":"additional","affiliation":[{"name":"National Center for Liver Cancer  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiu\u2010Liang","family":"Cui","sequence":"additional","affiliation":[{"name":"National Center for Liver Cancer  Shanghai China"},{"name":"International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute Naval Medical University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling\u2010Ting","family":"Guan","sequence":"additional","affiliation":[{"name":"National Center for Liver Cancer  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan\u2010Yu","family":"Hu","sequence":"additional","affiliation":[{"name":"National Center for Liver Cancer  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Can","family":"Chen","sequence":"additional","affiliation":[{"name":"International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute Naval Medical University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4709-3334","authenticated-orcid":false,"given":"Han","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pathology Eastern Hepatobiliary Surgery Hospital, Naval Medical University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiang\u2010Yu","family":"Wu","sequence":"additional","affiliation":[{"name":"National Center for Liver Cancer  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei\u2010Jia","family":"Zhang","sequence":"additional","affiliation":[{"name":"National Center for Liver Cancer  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pei\u2010Lin","family":"Zhang","sequence":"additional","affiliation":[{"name":"National Center for Liver Cancer  Shanghai China"},{"name":"International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute Naval Medical University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong\u2010Yang","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Metabolism &amp; 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