Mouse model of carbon tetrachloride induced liver fibrosis: Histopathological changes and expression of CD133 and epidermal growth factor

BMC Gastroenterology

Research Article

Gregory Y Lauwers¹  Yakup Kulu²  Tsutomu Fujii²  Kenneth K Tanabe²  Suguru Yamada²  Bryan C Fuchs²  Michael Lanuti³  Jonathan M Goodwin³ 

[1] Department of Pathology, Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, USA;Division of Surgical Oncology, Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, USA;Division of Thoracic Surgery, Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, USA;

关键词: Epidermal Growth Factor;    Glial Fibrillary Acidic Protein;    Proliferate Cell Nuclear Antigen;    Liver Regeneration;    Chronic Liver Injury;   

DOI  :  10.1186/1471-230X-10-79

 received in 2009-11-30, accepted in 2010-07-09,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundIn the setting of chronic liver injury in humans, epidermal growth factor (EGF) and EGF receptor (EGFR) are up-regulated and have been proposed to have vital roles in both liver regeneration and development of hepatocellular carcinoma (HCC). Chronic liver injury also leads to hepatic stellate cell (HSC) differentiation and a novel subpopulation of HSCs which express CD133 and exhibit properties of progenitor cells has been described in rats. The carbon tetrachloride (CCl4)-induced mouse model has been historically relied upon to study liver injury and regeneration. We exposed mice to CCl4 to assess whether EGF and CD133+ HSCs are up-regulated in chronically injured liver.MethodsCCl4 in olive oil was administered to strain A/J mice three times per week by oral gavage.ResultsMultiple well-differentiated HCCs were found in all livers after 15 weeks of CCl4 treatment. Notably, HCCs developed within the setting of fibrosis and not cirrhosis. CD133 was dramatically up-regulated after CCl4 treatment, and increased expression of desmin and glial fibrillary acidic protein, representative markers of HSCs, was also observed. EGF expression significantly decreased, contrary to observations in humans, whereas the expression of amphiregulin, another EGFR ligand, was significantly increased.ConclusionsSpecies-specific differences exist with respect to the histopathological and molecular pathogenesis of chronic liver disease. CCl4-induced chronic liver injury in A/J mice has important differences compared to human cirrhosis leading to HCC.

【 授权许可】

Unknown   
© Fujii et al; licensee BioMed Central Ltd. 2010. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.