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Biosci. (Landmark Ed)"],"abstract":"<jats:p>Background:Liver fibrosis is pathologically characterized by excessive extracellular matrix (ECM) deposition induced by diverse etiological factors, which is associated with hepatic stellate cell (HSC) activation and proliferation. B-cell translocation gene 1 (BTG1) contributes to the regulation of cellular proliferation, differentiation, and development. The biological role of BTG1 in HSC activation and liver fibrosis remains incompletely understood.Methods:To clarify the regulatory role of BTG1, carbon tetrachloride (CCl4)-induced rat liver fibrosis models and platelet-derived growth factor-BB (PDGF-BB)-activated HSC-T6 cells were used. For in vivo studies, rats were injected with BTG1-overexpressing recombinant adeno-associated virus (AAV). siRNA or overexpression vectors targeting BTG1 were transfected into HSC-T6 cells in vitro, respectively. Rat serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were measured using biochemical assays. Liver histopathological alterations were evaluated by histological staining. 5-ethynyl-2\u2032-deoxyuridine (EdU) assays and flow cytometry were used to assess cell proliferation and apoptosis. Immunohistochemistry, Western blotting, and quantitative real-time polymerase chain reaction (RT-qPCR) were performed to quantify the levels of \u03b1-smooth muscle actin (\u03b1-SMA), collagen I, interleukin-6 (IL-6), and tumor necrosis factor-\u03b1 (TNF-\u03b1), as well as proliferation- and apoptosis-related proteins. Furthermore, a specific JAK2 inhibitor was used to further clarify the underlying molecular mechanism.Results:BTG1 was significantly downregulated in CCl4-induced fibrotic liver tissues and activated HSCs. AAV-mediated BTG1 overexpression markedly alleviated liver fibrosis in rats. siRNA-mediated BTG1 knockdown resulted in the significant upregulation of collagen I, \u03b1-SMA, IL-6, and TNF-\u03b1 expression in HSC-T6 cells. BTG1 deficiency enhanced HSC-T6 cell proliferation induced by PDGF-BB as evidenced by increased expression of proliferating cell nuclear antigen (PCNA) and Ki67, while inhibiting apoptotic death, as evidenced by reduced levels of Bax and cleaved caspase-3, and by enhanced Bcl-2 expression. BTG1 overexpression had the opposite effects. Mechanistically, BTG1 deficiency enhanced JAK2\/STAT3 signaling by upregulating the phosphorylation of these signaling intermediaries, whereas BTG1 overexpression inhibited this signaling pathway. Notably, pretreatment with the JAK2 inhibitor ruxolitinib neutralized BTG1 knockdown-induced JAK2\/STAT3 hyperactivation.Conclusions:BTG1 suppresses HSC activation by modulating the JAK2\/STAT3 signaling axis and retards liver fibrosis progression, suggesting that it may represent a promising therapeutic target for anti-fibrotic intervention.<\/jats:p>","DOI":"10.31083\/fbl51017","type":"journal-article","created":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T12:17:49Z","timestamp":1785413869000},"source":"Crossref","is-referenced-by-count":0,"title":["BTG1 Mediates the Proliferation and Activation of Hepatic Stellate Cells via the JAK2\/STAT3 Pathway in Liver Fibrosis"],"prefix":"10.31083","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-2314-2615","authenticated-orcid":true,"given":"Weili","family":"Lu","sequence":"first","affiliation":[{"name":"Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, School of Pharmacy, Anhui Medical University, 230032 Hefei, Anhui, China"},{"name":"Department of Clinical Laboratory, The Second Hospital of Anhui Medical University, 230032 Hefei, Anhui, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziyi","family":"An","sequence":"additional","affiliation":[{"name":"Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, School of Pharmacy, Anhui Medical University, 230032 Hefei, Anhui, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muran","family":"Lu","sequence":"additional","affiliation":[{"name":"Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, School of Pharmacy, Anhui Medical University, 230032 Hefei, Anhui, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinling","family":"Kong","sequence":"additional","affiliation":[{"name":"Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, School of Pharmacy, Anhui Medical University, 230032 Hefei, Anhui, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Wang","sequence":"additional","affiliation":[{"name":"Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, School of Pharmacy, Anhui Medical University, 230032 Hefei, Anhui, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-3107-9658","authenticated-orcid":true,"given":"Xiaowen","family":"Feng","sequence":"additional","affiliation":[{"name":"Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, School of Pharmacy, Anhui Medical University, 230032 Hefei, Anhui, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5073-5799","authenticated-orcid":true,"given":"Fanrong","family":"Wu","sequence":"additional","affiliation":[{"name":"Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, School of Pharmacy, Anhui Medical University, 230032 Hefei, Anhui, China"},{"name":"Department of Clinical Laboratory, The Second Hospital of Anhui Medical University, 230032 Hefei, Anhui, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"16242","published-online":{"date-parts":[[2026,7,17]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","unstructured":"Kisseleva T, Brenner D. 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