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

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.

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.

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.

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.