Primary cirrhotic hepatocytes resist TGFβ-induced apoptosis through a ROS-dependent mechanism

Abstract Background/Aims The cirrhotic liver manifests dysregulated hepatocyte growth by poor regenerative capacity, formation of regenerative nodules, and malignant transformation to hepatocellular carcinoma. The purpose of this study was to determine if dysregulated hepatocyte growth occurs through deficient apoptosis. Methods Hepatocytes were isolated from normal and CCl 4 -treated mice and treated with TGFβ, TNFα, and UV-C, known apoptotic agents. Results Cirrhotic hepatocytes were less sensitive to TGFβ- (45±5 vs. 15±3%; P P =0.02), and UV-C-induced (31±4 vs. 17±4%; P Conclusions These findings suggest that increased ROS activity in cirrhotic hepatocytes plays a critical role in mediating cirrhotic hepatocyte resistance to apoptosis. Cirrhotic hepatocyte resistance to TGFβ-induced apoptosis is ROS-dependent and is a mechanism of dysregulated growth in the chronically inflamed liver.