P2X7 blockade attenuates mouse liver fibrosis

Abstract

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‑κB (NF‑κB) 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‑κB 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 α-smooth muscle actin and transforming growth factor‑β1. 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.