Elucidate Molecular Mechanisms of a New Drug on Liver Fibrosis

by Proteomics Analysis

　

Tzu-Ling Tseng, Ph.D.

Division of Molecular Biomedical Technology, Biomedical Engineering Research Laboratories, Industrial Technology Research Institute, Bldg. 53, 195 Sec.4, Chung Hsing Rd., Chutung, Hsinchu, Taiwan 310

Virus-induced chronic liver disease is a common and potential lethal problem in Asia. A liver fibrosis model together with state of the art differential profiling technologies, genes related to fibrotic injury was identified. Furthermore, we have applied the same technologies to elucidate the molecular mechanisms of a Chinese medicine, ZC008, which can reverse liver fibrosis. Here, we used dimethylnitrosamine (DMN) to induced rat necroinflammatory and hepatic fibrosis. The liver tissues of controls and DMN-treated and/or ZC 008-treated rates were used to perform iTRAQ labeling experiments. More than thousands of proteins could be quantified simultaneously. Hundreds of differentially expressed proteins were identified from the liver injury tissues. Western blotting carried out for further validation the results obtained by . To further refine the genes with differential expression in the fibrotic liver and fibrosis-related genes reversed by ZC008, we carried out network analysis using Ingenuity Analysis (IPA) software. Seventy-five of ninety-six proteins identified in the proteomic study at sixth week fall into 8 networks. Intriguingly, most of the fibrosis-related genes reversed by ZC008 were resided in three of eight networks mentioned above. In summary, we believe that molecular portraits of hepatic fibrosis from this study may provide novel biological insights into the development of early liver damaged and molecular classifiers that could be applied for clinical application of liver fibrosis.