Global gene expression profiling of dimethylnitrosamine-induced liver fibrosis: from pathological and biochemical data to microarray analysis.

14 The development of hepatocellular carcinoma is generally preceded by hepatic cirrhosis, which occurs at the end stage of fibrosis, which is a common and potentially lethal problem in chronic liver disease in Asia. The development of microarrays that permits us to monitor transcriptomes on a genome-wide scale has dramatically expedited a comprehensive understanding of the disease process. Here, we used dimethylnitrosamine (DMN), a potent hepatotoxin for necroinflammatory, to induce rat hepatic fibrosis. During the 6-week time course period, histopathological, biochemical and quantitative RT-PCR analyses, confirmed incidence of necroinflammatory and hepatic fibrosis in the established rat model system. By using Affymetrix microarry chip (RG-U34A), hierarchical clustering of samples correctly identified by both 1.5-fold change and flag selection, and then 273 differentially expressed genes were clustered in hepatic fibrosis tissues. Hierarchical clustering of gene expression levels identified several stage-characteristic, functionally related clusters, encoding proteins that were related to metabolism, cell growth and/or maintenance and response to external by gene ontology database (GO). Among these genes, there are 44 necroinflammatory-related and 62 fibrosis-related potential markers or drug targets. The molecular portraits of hepatic fibrosis in this study may provide novel biological insights for the development of earlier liver damage molecular classifiers.