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Through analysis of gene expression omnibus datasets and human fibrotic liver samples, we identified significant CXCR6 upregulation, subsequently validated in murine fibrosis models. Using quantitative real-time polymerase chain reaction, western blotting, and immunohistochemistry, we demonstrated that CXCR6 silencing\n                    <jats:italic>in vitro<\/jats:italic>\n                    promoted aHSC senescence \u2013 as confirmed by senescence-associated \u03b2-galactosidase staining and Cell Counting Kit-8 assays \u2013 while simultaneously restricting the pro-inflammatory senescence-associated secretory phenotype (SASP). Mechanistically, the enzyme-linked immunosorbent assay revealed this process involves modulation of the interleukin-1 alpha\/nuclear factor-kappa beta feedback loop. Our findings position CXCR6 inhibition as a promising therapeutic strategy that uniquely targets both fibrogenesis (through hepatic stellate cell senescence induction) and inflammation (via SASP regulation) in hepatic fibrosis.\n                  <\/jats:p>","DOI":"10.1515\/biol-2025-1151","type":"journal-article","created":{"date-parts":[[2025,8,8]],"date-time":"2025-08-08T09:58:11Z","timestamp":1754647091000},"source":"Crossref","is-referenced-by-count":2,"title":["Inhibiting CXCR6 promotes senescence of activated hepatic stellate cells with limited proinflammatory SASP to attenuate hepatic fibrosis"],"prefix":"10.1515","volume":"20","author":[{"given":"Liqin","family":"Sheng","sequence":"first","affiliation":[{"name":"Department of Infectious Diseases, Haiyan People\u2019s Hospital , Jiaxing , Zhejiang , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiming","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, The First Hospital of Jiaxing, Affiliated Hospital of Jiaxing University , Jiaxing , Zhejiang , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fei","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, The First Hospital of Jiaxing, Affiliated Hospital of Jiaxing University , 1882 Zhonghuan South Road, Nanhu District , Jiaxing , Zhejiang , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenzhou","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, The First Hospital of Jiaxing, Affiliated Hospital of Jiaxing University , 1882 Zhonghuan South Road, Nanhu District , Jiaxing , Zhejiang , China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"374","published-online":{"date-parts":[[2025,8,8]]},"reference":[{"key":"2025122123391951086_j_biol-2025-1151_ref_001","doi-asserted-by":"crossref","unstructured":"Iredale JP. 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