CCN5-Derived Peptide Ameliorates Liver Fibrosis in Mice through Inhibiting the ERK1/2 and PI3K Signaling Pathways.

Liver fibrosis is a pathological process characterized by the activation of hepatic stellate cells (HSCs) and the excessive accumulation of extracellular matrix (ECM) proteins. Cellular communication network 5 (CCN5) has been recently recognized for its ability to counteract the profibrotic effects of CCN2 in fibrotic diseases. Herein, we report the discovery of a CCN5-derived peptide CDP199 that effectively suppresses HSC activation and reduces ECM protein deposition. Notably, CDP199 exhibits strong inhibitory effects on HSC proliferation and migration. The subsequent in vivo study demonstrated that peptide CDP199 significantly alleviates liver injury, enhances liver function, and mitigates liver fibrosis in a carbon tetrachloride-induced mouse model. Mechanistically, CDP199 inhibits the phosphorylation of ERK1/2 and PI3K both in vitro and in vivo. These findings highlight the therapeutic potential of CCN5-derived peptides, specifically CDP199, as a promising antifibrotic candidate for treating liver diseases through inhibition of ERK1/2 and PI3K signaling pathways.