The antifibrotic effect of TGF-β1 siRNAs in murine model of liver cirrhosis

Abstract

Liver fibrosis results from chronic damage to the liver by chronic hepatitis, alcohol, and toxic agents. A characteristic of liver fibrosis is an accumulation of extracellular matrix (ECM) protein, which distorts the hepatic architecture by forming a fibrous scar, and the subsequent development of regenerating nodules defines cirrhosis. Transforming growth factor (TGF)-β1, one of the most powerful profibrogenic mediators, plays a major role in the development of liver cirrhosis and regulates ECM gene expression and matrix degradation. This study elucidates the changes of TGF-β1-mediated signals during liver fibrogenesis by using RNA interference. In this experiment, the TGF-β1 siRNAs reduced the expression of TGF-β1 in the livers of CCl4 injection compared with those of control group, and the expression of type I collagen and α-smooth muscle actin was decreased. In conclusion, this study demonstrates that TGF-β1 siRNAs inhibit TGF-β1 expression in the murine model of liver cirrhosis and might be a good therapeutic strategy to prevent liver cirrhosis in human.

Keywords TGF-β1; RNA interference; siRNA; Liver cirrhosis