Microarray analysis of hepatic gene expression during long-term cholestasis induced by common bile duct ligation in rats.

Cholestasis is one of the major liver diseases and results in progressive liver fibrosis and cirrhosis. In this study, the transcriptional response of the liver to common bile duct ligation in rats was examined by cDNA microarray analysis, and 134 genes for which expression was altered during long-term cholestasis were identified. Clustering analysis of these genes for multiple time-point data yielded 7 different patterns in which a large portion of the genes was classified into 3 clusters. Two clusters consisted of up-regulated genes, including genes that may be related to disruption of lipid metabolism and liver fibrosis observed in the early stage of cholestasis, and the other cluster consisted of down-regulated genes, including a gene that has been thought to be involved in the mechanism of cell protection against accumulation of bile acids. Since the expression patterns of these genes appear to reflect molecular features of cholestasis. Characterization of the genes identified in this study may shed further light on the physiological and pathological characteristics of long-term cholestasis.