A20 rescues hepatocytes from apoptosis through the NF-κB signaling pathway in rats with acute liver failure

Abstract

Abstract Background: Acute liver failure (ALF) is a disease of acute derangements in the hepatic synthetic function with defects involving innate immune responses, which was reported to be negatively regulated by tumor necrosis factor α-induced protein 3 (A20). Herein, the present study was conducted to investigate the effects the A20 protein on the proliferation and apoptosis of hepatocytes through the nuclear factor (NF)-κB signaling pathway in the rat models simulating ALF. Methods: Male Wistar rats were used to simulate ALF in the model rats. Next, the positive expression of A20 and Caspase-3 proteins was measured in liver tissues. Rat hepatocytes were separated and subjected to pyrrolidine dithiocarbamate (PDTC, inhibitor of NF-κB pathway) or A20 siRNA. Additionally, both mRNA and protein levels of A20, NF-κB, tumor necrosis factor (TNF) receptor-associated factor 6 (TRAF6), and receptor-interacting protein 1 (RIP1) were determined. Finally, we detected the hepatocyte proliferation, cell cycle entry, and apoptosis. Results: ALF rats displayed a lower positive expression of A20 protein and a higher expression of Caspase-3 protein. Furthermore, A20 was down-regulated, while NF-κB, TRAF6, and RIP1 were all up-regulated in ALF rats. Notably, A20 inhibited activation of NF-κB signaling pathway. The blockade of NF-κB signaling pathway enhanced proliferation and cell cycle progression of hepatocytes, whereas inhibited apoptosis of hepatocytes. On the contrary, A20 siRNA reversed the above situation. Conclusion: A20 inhibits apoptosis of hepatocytes and promotes the proliferation through the NF-κB signaling pathway in ALF rats, potentially providing new insight into the treatment of ALF.