Fig. 1.

STING knockout and pharmacological inhibition attenuate liver fibrosis and hepatic inflammation

(A-B) Wild-type mice were injected with olive oil or CCl₄ for 6 weeks. Enriched signaling pathway analysis of upregulated (CCl₄vs. olive oil) DEGs (A) and the heatmap of target DEGs (B) from RNA-sequencing were analyzed (n = 3/group). (C) Seven normal human livers and 11 cirrhotic human livers were collected. The distribution and protein levels of STING, t-IRF3, and p-IRF3 were analyzed by IHC or WB. (D–G)Sting^+/+ and Sting^−/− mice were injected with olive oil or CCl₄ for 6 weeks (n = 6/group). Liver fibrosis was analyzed by Sirius red staining, IF, and WB for collagen I and αSMA. (H) RNA-sequencing was performed in CCl₄-treated Sting^+/+ and Sting^−/− mice. Enriched pathway analysis of downregulated DEGs (Sting^−/−vs. Sting^+/+) was performed (n = 3/group). (I–L) Wild-type mice were treated with either olive oil or CCl₄ for 6 weeks in addition to either vehicle or STING inhibitor C-176 (20 mg/kg, n = 6/group). Liver fibrosis was analyzed by Sirius red staining, IF, and WB for collagen I and αSMA. (M–N) The protein levels and activity of CYP2E1 were detected by IF (M) and activity kit (N). *p < 0.05, **p < 0.01, ***p < 0.001. (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article.)