title: [Augmenter of liver regeneration promotes the proliferation of HL-7702 cells in carbon tetrachloride-induced acute liver injury via increasing autophagy].
abstract: 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+CCl4intervention group, 3-methyladenine (3-MA)+CCl4intervention group, and ALR+3-MA+CCl4intervention group. The ALR+CCl4and ALR+3-MA+CCl4intervention groups were transfected with ALR plasmids at 8 hours before CCl4treatment. All groups except the normal control group were treated with CCl4, and 30 minutes later, the 3-MA+CCl4and ALR+3-MA+CCl4intervention groups were treated with 3-MA. The cells were collected at 24 hours after CCl4treatment. 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+CCl4intervention group had significant increases in the protein and mRNA expression of ALR compared with the acute liver injury group (bothP< 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 (bothP< 0.05). Compared with the CCl4-induced acute liver injury group, the ALR+CCl4intervention 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+CCl4intervention group had a significant reduction in the expression of regeneration-associated proteins compared with the ALR+CCl4intervention group, while there was no significant difference between the ALR+3-MA+CCl4intervention group and 3-MA+CCl4intervention 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.
authors.affiliation: Capital Medical University Beijing You'an Hospital Artificial Liver Center, Beijing 100069, China.
authors.forename: W J
authors.initials: WJ
authors.lastname: Han
authors.affiliation: Beijing Liver Disease Research Institute, Beijing 100069, China.
authors.forename: H B
authors.initials: HB
authors.lastname: Shi
authors.affiliation: Beijing Liver Disease Research Institute, Beijing 100069, China.
authors.forename: H L
authors.initials: HL
authors.lastname: Shi
authors.affiliation: Shanxi Medical University, Taiyuan 030001, China.
authors.forename: J Y
authors.initials: JY
authors.lastname: Song
authors.affiliation: Beijing Liver Disease Research Institute, Beijing 100069, China.
authors.forename: F
authors.initials: F
authors.lastname: Ren
authors.affiliation: Capital Medical University Beijing You'an Hospital Artificial Liver Center, Beijing 100069, China.
authors.forename: Z P
authors.initials: ZP
authors.lastname: Duan
authors.affiliation: Capital Medical University Beijing You'an Hospital Artificial Liver Center, Beijing 100069, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Chen
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives; D000410:Alanine Transaminase; D001219:Aspartate Aminotransferases; D001343:Autophagy; D002251:Carbon Tetrachloride; D056486:Chemical and Drug Induced Liver Injury / Q000378:metabolism / Q000473:pathology*; D022781:Hepatocytes; D006801:Humans; D008099:Liver; D017114:Liver Failure, Acute / Q000378:metabolism; D008115:Liver Regeneration; D050862:Oxidoreductases Acting on Sulfur Group Donors / Q000378:metabolism*; D018809:Proliferating Cell Nuclear Antigen / Q000097:blood; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D018809:Proliferating Cell Nuclear Antigen; C025946:3-methyladenine; D002251:Carbon Tetrachloride; C500897:GFER protein, human; D050862:Oxidoreductases Acting on Sulfur Group Donors; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D000225:Adenine