C23 ameliorates carbon tetrachloride-induced liver fibrosis in mice

BACKGROUND C23, an oligo-peptide derived from cold-inducible RNA-binding protein (CIRP), has been reported to inhibit tissue inflammation, apoptosis and fibrosis by binding to the CIRP receptor; however, there are few reports on its role in liver fibrosis and the underlying mechanism is unknown. AIM To explore whether C23 plays a significant role in carbon tetrachloride (CCl4)-induced liver fibrosis. METHODS CCl4 was injected for 6 weeks to induce liver fibrosis and C23 was used beginning in the second week. Masson and Sirius red staining were used to examine changes in fiber levels. Inflammatory factors in the liver were detected and changes in alpha-smooth muscle actin (alpha-SMA) and collagen I expression were detected via immunohistochemical staining to evaluate the activation of hematopoietic stellate cells (HSCs). Western blotting was used to detect the activation status of the transforming growth factor-beta (TGF-beta)/Smad3 axis after C23 treatment. RESULTS CCl4 successfully induced liver fibrosis in mice, while tumor necrosis factor-alpha (TNF-alpha), IL (interleukin)-1 beta, and IL-6 levels increased significantly and the IL-10 level decreased significantly. Interestingly, C23 inhibited this process. On the other hand, C23 significantly inhibited the activation of HSCs induced by CCl4, which inhibited the expression of alpha-SMA and the synthesis of collagen I. In terms of mechanism, C23 can block Smad3 phosphorylation significantly and inhibits TGF-beta/Smad3 pathway activation, thereby improving liver injury caused by CCl4. CONCLUSION C23 may block TGF-beta/Smad3 axis activation, inhibit the expression of inflammatory factors, and inhibit the activation of HSCs induced by CCl4, alleviating liver fibrosis.