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

作者：Li, Ke-Zhi; Liao, Zhi-Yi; Li, Yu-Xuan; Ming, Zhi-Yong; Zhong, Jian-Hong; Wu, Guo-Bin; Huang, Shan^*; Zhao, Yin-Ning^*

来源：Bioscience Reports, 2019, 39(1): BSR20180316.

DOI：10.1042/BSR20180316

• FULMINANT HEPATIC-FAILURE
• MICE
• PATHOGENESIS
• INHIBITION
• DEFICIENCY
• ACTIVATION
• EXPRESSION
• MANAGEMENT
• INJURY
• CELLS

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 proportional to-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)-kappa B 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-kappa B pathway) or A20 siRNA. Additionally, both mRNA and protein levels of A20, NF-kappa B, 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-kappa B, TRAF6, and RIP1 were all up-regulated in ALF rats. Notably, A20 inhibited activation of NF-kappa B signaling pathway. The blockade of NF-kappa B 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-kappa B signaling pathway in ALF rats, potentially providing new insight into the treatment of ALF.

• 出版日期2019-1-31
• 单位广西医科大学