Original Article
Copyright ©2013 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Jun 28, 2013; 19(24): 3802-3809
Published online Jun 28, 2013. doi: 10.3748/wjg.v19.i24.3802
Role of activin A in carbon tetrachloride-induced acute liver injury
Dong-Hui Wang, Yi-Nan Wang, Jing-Yan Ge, Hai-Yan Liu, Hong-Jun Zhang, Yan Qi, Zhong-Hui Liu, Xue-Ling Cui
Dong-Hui Wang, Jing-Yan Ge, Yan Qi, Zhong-Hui Liu, Han-Yan Liu, Department of Immunology, Norman Bethune College of Medicine, Jilin University, Changchun 130021, Jilin Province, China
Yi-Nan Wang, Translational Medical Research Institute, First Hospital of Jilin University, Changchun 130061, Jilin Province, China
Hong-Jun Zhang, Department of Immunology, Mudanjiang Medical University, Mudanjiang 157011, Heilongjiang Province, China
Xue-Ling Cui, Department of Genetics, Norman Bethune College of Medicine, Jilin University, Changchun 130021, Jilin Province, China
Author contributions: Wang DH and Wang YN contributed equally to this work; Wang DH, Ge JY, Liu HY and Qi Y participated in the animals experiments, collected data and performed the statistical calculations; Cui XL participated in the animals experiments and drafting the manuscript; Wang YN, Zhang HJ and Liu ZH participated in the design of the study, performed literature searches and drafted the manuscript; all authors read and approved the final manuscript.
Supported by The Natural Science Foundation of China, Grants No. 30801005, No. 81273199 and No. 81270513; and the Project of Science and Development of Jilin Province (to Liu ZH)
Correspondence to: Dr. Xue-Ling Cui, Department of Genetics, Norman Bethune College of Medicine, Jilin University, 126 Xinmin Street, Changchun 130021, Jilin Province, China. cxl@jlu.edu.cn
Telephone: +86-431-85619476 Fax: +86-431-85639362
Received: February 16, 2013
Revised: April 12, 2013
Accepted: May 8, 2013
Published online: June 28, 2013
Abstract

AIM: 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.

CONCLUSION: 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.

Keywords: Liver injury, Carbon tetrachloride, Activin A, Immunohistochemistry

Core tip: The objective of this study was to investigate the expression and role of activin A in acute liver injury. A carbon tetrachloride (CCl4)-induced acute liver injury mouse model was used. Liver injury effects were examined by measuring alanine aminotransferase and aspartate aminotransferase levels in serum and liver pathological changes. Activin A protein expression levels were detected by enzyme-linked immunosorbent assay and immunohistochemistry. Activin type IIA receptor and Smad3 expressions in liver were analyzed by real-time quantitative reverse transcription-polymerase chain reaction. We found that activin A is involved in CCl4-induced acute liver injury, suggesting activin A could be a potential therapeutic option for acute liver injury diseases.