Korean J Hepatol > Volume 12(1); 2006 > Article
The Korean Journal of Hepatology 2006;12(1): 93-102.
Protein Expression Profiles in a Rat Cirrhotic Model Induced by Thioacetamide
Jeung Hee An, Ph.D.1,3, Jinsil Seong, M.D.1,3, Haejin Oh, M.S.1,3, Wonwoo Kim, M.S.1,3, Kwang-Hyub Han, M.D.2,3 and Yong Han Paik, M.D.2
Department of Radiation Oncology1, Liver Cirrhosis Clinical Research Center2, Brain Korea, 21 Project for Medical Science3, Yonsei University Medical College, Seoul, Korea
ABSTRACT
Background/Aims
The reactive oxygen species from thioacetamide (TAA) induces rat liver cirrhosis that resembles the human disease, and it can serve as a suitable animal model for studying human liver cirrhosis. The aim of this study was to identify the molecular protein signatures via a proteomics approach with using a rat model with TAA-induced liver cirrhosis. Methods: Male Wistar rats were treated with 0.3 g/L TAA in their drinking water. The animals were then sacrificed at 9 and 30 weeks after TAA administration. The development of liver cirrhosis was observed with histological study. The livers were processed for proteins extraction and the proteins were analyzed by 2-dimensional electrophoresis. The proteins were identified by matrix-assisted laser desorption ionizing time-of-flight mass spectrometry and this was validated by immunohistochemical staining. Results: On the proteomics analysis of the liver tissues, a total of 88 proteins showed significant change in their expression between the controls and the cirrhotic rats. When the proteins were categorized by their function, they included ECM/cellular skeleton, cell proliferation/death signal, metabolism, DNA damage/stress and immune response related proteins. The level of expression gradually increased up to 30 weeks for interleukin-6 (IL-6) precursor, transforming growth factor-beta (TGF-β) induced protein, TIMP-1 and MMP-9. Cytochrome P450 2B, which is required for the metabolic activation of TAA, also showed the same increasing pattern. In contrast, the expression level of the proteins did not show a significant change at 9 weeks, but this increased to 3-fold at 30 weeks for carbonic anhydrase VII, ras related protein Rab 6, Annexin A2, neurofibromatosis type 2 and aldehyde dehydrogenase. Conclusions: This study showed that there is a repertoire of proteins during the development of liver cirrhosis via TAA. In this model, IL-6, TGF-β, MMP-9 and TIMP-1 were reconfirmed as the molecular signatures during the development of TAA-induced liver cirrhosis. (Korean J Hepatol 2006;12:93-102)
KeyWords: Proteomics, Cirrhosis, Thioacetamide, Rats

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