肝再生増強因子は自食レベルを増加することによりCCL_4誘導急性肝障害におけるHL-7702細胞の増殖を促進する。【JST・京大機械翻訳】

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. Key words: Liver regeneration; Liver injury, acute; Augmenter of liver regeneration; Autophagy