Figure 1.

The role of NOXs in myofibroblasts activation. The interactions between hepatocytes, Kupffer cells and HSCs promotes myofibroblast activation. Various NOX isoforms expressed in different cell types in the liver play crucial roles during this process. After exposure to hepatic insults, such as ischaemia/reperfusion (IR) injuries, alcohol abuse, viral infection, hyper-nutrition, and cholestasis, ROS is produced through NOXs in hepatocytes. Increased oxidative stress also induces hepatocyte apoptosis/necrosis, resulting in release of DAMPs that activate Kupffer cells. Injured hepatocytes and activated Kupffer cells secrete proinflammatory and profibrogenic cytokine TGFβ, which promotes the differentiation of HSCs into myofibroblasts (see text for further details).