rSjP40 Inhibited the Activity of Collagen Type I Promoter via Ets-1 in HSCs

Abstract

Liver fibrosis is a severe disease characterized by excessive deposition of extracellular matrix (ECM) components in the liver. Activated hepatic stellate cells (HSCs) are a major source of ECM and a key regulator of liver fibrosis. Collagen type I alpha I (COL1A1) is one of the main components of ECM and is a major component in fibrotic tissues. Previously, we demonstrated that soluble egg antigen from <i>Schistosoma japonicum</i> could inhibit the expression of COL1A1 in activated HSCs. In addition, studies have found that Ets proto-oncogene 1 (Ets-1) suppresses the production of ECM by down-regulating matrix related genes such as <i>COL1A1</i> induced by transforming growth factor β, and ultimately inhibits liver fibrosis. In this study, the major aim was to investigate the effect and mechanism of Ets-1 on inhibiting <i>COL1A1</i> gene promoter activity in HSCs by recombinant <i>Schistosoma japonicum</i> protein P40 (rSjP40). We observed the rSjP40 inhibited the expression of <i>COL1A1</i> by inhibiting the activity of the <i>COL1A1</i> promoter, and the core region of rSjP40 acting on <i>COL1A1</i> promoter was located at -1,722/-1,592. In addition, we also demonstrated that rSjP40 could promote the expression of Ets-1, and Ets-1 has a negative regulation effect on the <i>COL1A1</i> promoter in human LX-2 cells. These data suggest that rSjP40 might inhibit the activity of <i>COL1A1</i> promoter and inhibit the activation of HSCs by increasing the expression of transcription factor Ets-1, which will provide a new experimental basis for the prevention and treatment of liver fibrosis.