[Augmenter of liver regeneration promotes the proliferation of HL-7702 cells in carbon tetrachloride-induced acute liver injury via increasing autophagy].

Objective: To investigate the protective effect of augmenter of liver regeneration (ALR) against acute liver injury and related mechanisms. Methods: HL-7702 cells were divided into normal control group, carbon tetrachloride (CCl4)-induced acute liver injury group, ALR+CCl4 intervention group, 3-methyladenine (3-MA)+CCl4 intervention group, and ALR+3-MA+CCl4 intervention group. The ALR+CCl4 and ALR+3-MA+CCl4 intervention groups were transfected with ALR plasmids at 8 hours before CCl4 treatment. All groups except the normal control group were treated with CCl4, and 30 minutes later, the 3-MA+CCl4 and ALR+3-MA+CCl4 intervention groups were treated with 3-MA. The cells were collected at 24 hours after CCl4 treatment. The HL-7702 cells and supernatant were collected to measure the levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) (IU/L). Western blot was used to measure the levels of ALR, cyclin D, cyclin E, proliferating cell nuclear antigen (PCNA), autophagy-related gene 7 (Atg7), and autophagy genes LC3, p62, and Beclin-1. Quantitative real-time PCR was used to measure the mRNA expression of ALR. A one-way analysis of variance was used for comparison of means between any two groups. Results: The ALR+CCl4 intervention group had significant increases in the protein and mRNA expression of ALR compared with the acute liver injury group (both P < 0.05). The CCl4-induced acute liver injury group had significant increases in the protein and mRNA expression of ALR compared with the normal control group (both P < 0.05). Compared with the CCl4-induced acute liver injury group, the ALR+CCl4 intervention group had significant reductions in ALT (0.73±0.17 IU/L vs 1.43±0.38 IU/L, P < 0.05) and AST (19.85±1.83 IU/L vs 56.73±6.25 IU/L, P < 0.05) in supernatant, significantly increased expression of cyclin D, cyclin E, PCNA, LC3, Atg7, and Beclin-1 in hepatocytes, and significantly reduced expression of p62, which suggested that ALR protected the liver against acute liver injury, promoted the regeneration of hepatocytes, and enhanced the autophagy of hepatocytes. The ALR+3-MA+CCl4 intervention group had a significant reduction in the expression of regeneration-associated proteins compared with the ALR+CCl4 intervention group, while there was no significant difference between the ALR+3-MA+CCl4 intervention group and 3-MA+CCl4 intervention group, which suggested that after the inhibition of autophagy, there were significant reductions in the regeneration of hepatocytes and liver regeneration promoted by ALR. Conclusion: ALR can promote the regeneration of hepatocytes in liver parenchyma, which is achieved by the regulation of autophagy.