Inhibiting CXCR6 promotes senescence of activated hepatic stellate cells with limited proinflammatory SASP to attenuate hepatic fibrosis
Year: 2025
Type: article
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). 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.
Source: Open Life Sciences
Authors: Liqin Sheng, Yiming Wu, Fei Shen, Chenzhou Xu
Institutions: Jiaxing University, First Hospital of Jiaxing
Language: English
Subfield: Hepatology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,373
OpenAlex ID: W4413249752