Inhibiting CXCR6 promotes senescence of activated hepatic stellate cells with limited proinflammatory SASP to attenuate hepatic fibrosis.

ABSTRACT: This study investigates the previously unexplored role of CXC chemokine receptor 6 (CXCR6) in hepatic fibrosis, where excessive extracellular matrix deposition by activated hepatic stellate cells (aHSCs) drives disease progression. 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 in vitro promoted aHSC senescence - as confirmed by senescence-associated β-galactosidase staining and Cell Counting Kit-8 assays - while simultaneously restricting the pro-inflammatory senescence-associated secretory phenotype (SASP). Mecha

SUBMITTER: Sheng L 

PROVIDER: S-EPMC12355364 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature