Ppic modulates CCl4-induced liver fibrosis and TGF-β-caused mouse hepatic stellate cell activation and regulated by miR-137-3p.

Hepatic stellate cell activation, characterized by hyperproliferation and increased release of collagens, is a critical event during the initiation and development of hepatic fibrosis. The deregulated genes among different expression profiles based on online datasets were analyzed, attempting to identify novel potential biomarkers and treatment targets for hepatic fibrosis. The abnormal upregulation of mouse peptidylprolyl isomerase C (Ppic) within the CCl4-caused hepatic fibrosis model in mice was identified according to bioinformatics and experimental analyses. The knockdown of Ppic in the CCl4-caused liver fibrosis murine model significantly improved CCl4-caused liver damage, decreased the fibrotic area, reduced ECM deposition, and reduced the hydroxyproline levels. The knockdown of Ppic in TGF-β-stimulated mouse hepatic stellate cells inhibited cell proliferation and decreased ECM levels. Through direct targeting, miR-137-3p negatively regulated Ppic expression. Contrastingly to Ppic knockdown, miR-137-3p inhibition further promoted cell proliferation and boosted ECM levels; the effects of miR-137-3p inhibition could be partially reversed by Ppic knockdown. Altogether, mmu-miR-137-3p directly targets Ppic and forms a regulatory axis with Ppic, modulating CCl4-caused hepatic fibrosis in mice and TGF-β-caused mouse hepatic stellate cell activation.