P2X7 blockade attenuates mouse liver fibrosis

P2X7 is important in inflammation and tissue injury. The aim of the present study was to investigate the effect of P2X7 inhibition, using a specific inhibitor (A438079) to prevent the development of liver injury and fibrosis in a mouse model of liver fibrosis. The mouse liver fibrosis model was induced by carbon tetrachloride (CCl4). Mice received subcutaneous administration of vehicle (saline/olive oil), CCl4 or subcutaneous CCl4 and A438079. The pro-inflammatory and pro-fibrotic factors were determined by western blot analysis. The biochemistry, histopathology, collagen deposition and nuclear factor-B (NF-B) activity were also analyzed. Chronic CCl4 treatment resulted in liver injury and collagen accumulation. The expression levels of P2X7, pro-inflammatory and pro-fibrotic mediators, and the activity of NF-B were markedly increased. Treatment with A438079 significantly inhibited CCl4-induced P2X7 expression, and attenuated CCl4-induced liver injury and the inflammatory response. P2X7 blockade also significantly reduced the formation of collagen in the liver and the expression of -smooth muscle actin and transforming growth factor-1. This study demonstrated that P2X7 inhibition attenuated liver injury and fibrosis in a mouse model. Thus, P2X7 is a potential novel therapeutic target for liver injury and fibrosis.