Catalase ameliorates hepatic fibrosis by inhibition of hepatic stellate cells activation.

Abstract

Catalase, an endogenous antioxidant enzyme, is thought to have rescue effects on hepatic fibrosis. In this study, the regulation of catalase in CCl₄-induced hepatic fibrogenesis was investigated. Our results indicated that catalase expression was decreased upon CCl₄ treatment in a time-dependent manner, while the expression of several profibrosis and proangiogenic factors, including transforming growth factor (TGF)-beta 1, vascular endothelial growth factor (VEGF), and angiopoietin 1 were significantly increased. To assess the role of catalase in hepatic fibrosis, catalase was overexpressed in HSC-T6 cells. This overexpression resulted in the inhibition of cell proliferation, migratory activity, and alpha-smooth muscle actin (alpha-SMA) expression, key features that characterize activation of hepatic stellate cells (HSC). Overexpression of catalase led to a decrease in the secretion of collagen type 1 and angiopoietin 1. These results indicate that loss of catalase activity is involved in the pathogenesis of hepatic fibrosis caused by the activation of HSCs.