title: Role of activin A in carbon tetrachloride-induced acute liver injury.
abstract: OBJECTIVE
  To investigate the expression and role of activin A in a mouse model of acute chemical liver injury.
  
  
  METHODS
  Acute liver injury in C57BL/6 male mice was induced by intraperitoneal injection with carbon tetrachloride (CCl4) (0.5 mL/kg, body weight) dissolved in olive oil (1:19 v/v). Mice were sacrificed 1, 3, 5 and 7 d after the treatment. The levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in serum were examined and pathological changes of liver observed by hematoxylin and eosin staining to evaluate the liver injury. Activin A protein levels in serum and hepatic tissue homogenate of mice were detected by enzyme-linked immunosorbent assay, and the expression pattern of activin A protein in livers of mice was examined by immunohistochemistry. Activin type IIA receptor (ActRIIA) and Smad3 expressions in the liver were analyzed by real-time quantitative reverse transcription-polymerase chain reaction. In order to further investigate the role of activin A, we also utilized activin A blocking experiment by anti-activin A antibody (500 μg/kg, body weight) injection into mouse tail vein.
  
  
  RESULTS
  In CCl4-treated mice, serum ALT and AST levels were significantly increased, compared with that in control mice (P < 0.01). Furthermore, the serious necrosis was observed around hepatic portal areas in CCl4-treated mice. Simultaneously, activin A levels in serum and hepatic tissue homogenate of mice treated with CCl4 for 1, 3 and 5 d increased significantly, compared with that in control mice (P < 0.01). Activin A protein expression in hepatocytes not within the necrotic area was also upregulated in mice following CCl4 treatment. Not only activin A, but also ActRIIA and activin signaling molecule Smad3 mRNA expressions in injury liver induced by CCl4 were significantly higher than that in control liver. In addition, levels of serum ALT and AST in CCl4-treated mice were significantly decreased by injection of anti-activin A antibody to block endogenous activin A action, compared with that in CCl4-treated mice by injection of immunoglobulin G instead of anti-activin A antibody (P < 0.01), and the severity of liver injury was also reduced remarkably.
  
  
  CONCLUSIONS
  These data show that activin A is involved in CCl4-induced acute liver injury. Blocking activin A actions may be a therapeutic approach for acute liver injury.
authors.affiliation: Department of Immunology, Norman Bethune College of Medicine, Jilin University, Changchun 130021, Jilin Province, China.
authors.forename: Dong-Hui
authors.initials: DH
authors.lastname: Wang
authors.forename: Yi-Nan
authors.initials: YN
authors.lastname: Wang
authors.forename: Jing-Yan
authors.initials: JY
authors.lastname: Ge
authors.forename: Hai-Yan
authors.initials: HY
authors.lastname: Liu
authors.forename: Hong-Jun
authors.initials: HJ
authors.lastname: Zhang
authors.forename: Yan
authors.initials: Y
authors.lastname: Qi
authors.forename: Zhong-Hui
authors.initials: ZH
authors.lastname: Liu
authors.forename: Xue-Ling
authors.initials: XL
authors.lastname: Cui
mesh_terms: D028341:Activins / Q000502:physiology*; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D002251:Carbon Tetrachloride / Q000009:adverse effects*; D056486:Chemical and Drug Induced Liver Injury / Q000378:metabolism / Q000503:physiopathology*; D004195:Disease Models, Animal; D008099:Liver / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015398:Signal Transduction / Q000502:physiology*; D051785:Smad Proteins / Q000502:physiology
chemical_list: D051785:Smad Proteins; C422405:activin A; D028341:Activins; D002251:Carbon Tetrachloride; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase
keywords: Activin A; Carbon tetrachloride; Immunohistochemistry; Liver injury