Potential biomarker discovery revealing the mechanism of reversal in the DMN-induced rat reversible liver fibrosis
Date Issued
2010
Date
2010
Author(s)
Lin, Ting-Chia
Abstract
The aim of study is to compare protein expression profile between reversible and irreversible liver fibrosis in DMN-induced rat model and find out the pivotal pathway regulating the development of liver fibrosis. In this study, DMN (Dimethylnitrosamine), carcinogen, was used to induce liver fibrosis in rat. The degree of liver fibrosis was determined by histological analysis of liver sections. Immunohistochemistry stain of liver sections was performed in different liver fibrosis stages for timing definition of reversible and irreversible liver fibrosis in the DMN-induced rat model. Collecting the rat serum in different stages of fibrosis followed by proteomic analysis, which included 2DE (two-dimensional electrophoresis)、In-gel digestion and matrix-assisted laser desorption/ionization mass spectrometry. The differentially expressed protein spots were analyzed by computer-assisted image analysis (PDQEST) software (p<0.05). Identified proteins included Hp (haptoglobin), ApoE (apolipoprotein E) and complement C3. Based on the identified proteins, MetacoreTM was applied to organize network relevant to the identified proteins. The bioinformatics tool-based analyzed result shows Alternative complement pathway might be associated with the reversible regulation of liver fibrosis. Complement C3 is regard as a pivotal factor regulating the proliferation of hepatocyte. The result indicated complement C3 might be an of importance factor regulating the development of liver fibrosis, up to now, no studies elucidate the role of complement C3 in the reversibility of liver fibrosis. We also found MMPs and TIMPs involved in complement C3 regulated pathway. The functional role of MMPs and TIMPs in liver fibrosis was studied in a number of previous researches, but detail still not completely understood. Taken together, complement C3 might serve as a notable mediator involved in reversibility of liver fibrosis.
Subjects
DMN-induced rat liver fibrosis
2-DE
immunohistochemistry stain
complement component 3
MMPs
TIMPs
hepatocyte proliferation
Type
thesis
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