title: Augmenter of liver regeneration protects against carbon tetrachloride-induced liver injury by promoting autophagy in mice.
abstract: BACKGROUND
  Augmenter of liver regeneration (ALR) exerts strong hepatoprotective properties in various animal models of liver injury, but its protective mechanisms have not yet been explored. Autophagy is a recently recognized rudimentary cellular response to inflammation and injury. The aim of this study was to test the hypothesis that ALR may protect against acute liver injury through the autophagic pathway.
  
  
  METHODS
  The level and role of ALR in liver injury were studied in a mouse model of acute liver injury induced by carbon tetrachloride (CCl4). The effect of ALR on autophagy was analyzed in vitro and in vivo. After autophagy was inhibited by 3-methyladenine (3-MA), apoptosis and proliferation were detected in the mouse model with acute liver injury. The ALR and autophagic levels were measured in patients with liver cirrhosis (LC) and acute liver failure (ALF), respectively.
  
  
  RESULTS
  During the progression of acute liver injury, the ALR levels increased slightly in early stage and significantly decreased in late stage in mice. Treatment with an ALR plasmid via tail vein injection protected mice against acute liver injury. The protective effect of ALR relied on the induction of autophagy, which was supported by the following evidence: (1) ALR overexpression directly induced autophagy flux in vitro and in vivo; and (2) ALR treatment suppressed apoptosis and promoted proliferation in mice exposed to CCl4, but the inhibition of autophagy reversed these effects. More importantly, the ALR levels decreased in patients with LC and ALF compared with normal controls.
  
  
  CONCLUSIONS
  We demonstrated that ALR ameliorated liver injury via an autophagic mechanism, which indicates a potential therapeutic application for liver injury.
authors.affiliation: Beijing Youan Hospital, Capital Medical University, Beijing, China.|Beijing Institute of Hepatology, Capital Medical University, Beijing, China.
authors.forename: Hongbo
authors.initials: H
authors.lastname: Shi
authors.affiliation: Beijing Youan Hospital, Capital Medical University, Beijing, China.
authors.forename: Weijia
authors.initials: W
authors.lastname: Han
authors.affiliation: Beijing Youan Hospital, Capital Medical University, Beijing, China.|Beijing Institute of Hepatology, Capital Medical University, Beijing, China.
authors.forename: Honglin
authors.initials: H
authors.lastname: Shi
authors.affiliation: Beijing Youan Hospital, Capital Medical University, Beijing, China.|Beijing Institute of Hepatology, Capital Medical University, Beijing, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Ren
authors.affiliation: Beijing Youan Hospital, Capital Medical University, Beijing, China.|Beijing Institute of Hepatology, Capital Medical University, Beijing, China.
authors.forename: Dexi
authors.initials: D
authors.lastname: Chen
authors.affiliation: Beijing Youan Hospital, Capital Medical University, Beijing, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Beijing Youan Hospital, Capital Medical University, Beijing, China.|Beijing Institute of Hepatology, Capital Medical University, Beijing, China.
authors.forename: Zhongping
authors.initials: Z
authors.lastname: Duan
mesh_terms: D000818:Animals; D001343:Autophagy / Q000502:physiology*; D015153:Blotting, Western; D002251:Carbon Tetrachloride / Q000633:toxicity; D056486:Chemical and Drug Induced Liver Injury / Q000378:metabolism / Q000473:pathology*; D004195:Disease Models, Animal; D006801:Humans; D008103:Liver Cirrhosis / Q000378:metabolism; D008107:Liver Diseases / Q000378:metabolism / Q000473:pathology*; D017114:Liver Failure, Acute / Q000378:metabolism; D008297:Male; D008807:Mice, Inbred BALB C; D046529:Microscopy, Electron, Transmission; D008856:Microscopy, Fluorescence; D050862:Oxidoreductases Acting on Sulfur Group Donors / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D002251:Carbon Tetrachloride; D050862:Oxidoreductases Acting on Sulfur Group Donors; C551231:GFER protein, mouse
keywords: Pathology Section; apoptosis; augmenter of liver regeneration; autophagy; liver injury; proliferation