Extracellular matrix metabolism-related gene expression in bile duct-ligated rats

Bile duct-ligated rats have been widely used as a model of cholestatic liver fibrosis. The aim of this study was to analyze the sequential expression of extracellular matrix (ECM) metabolism-related genes in these rats. We analyzed the intrahepatic messenger RNA (mRNA) expression of several ECM metabolism-related genes: transforming growth factor β1 (TGF-β1), connective tissue growth factor (CTGF), procollagen-α1 (collagen-I), matrix metalloproteinase (MMP)-2, MMP-13 and tissue inhibitor of metalloproteinases (TIMP)-1 on days 10, 21 and 42 after bile duct ligation (BDL). A DNA microarray was used to evaluate the expression of genes related to early fibrogenesis on day 10 following BDL; the grade of hepatic fibrosis was found to gradually progress from day 10 to 42. Collagen-I mRNA expression significantly increased from day 10 to day 42, as did TGF-β1 and CTGF mRNA. On the other hand, MMP-13 and -2 mRNA expression increased maximally from day 10 to 21, but tended to decrease by day 42. TIMP-1 mRNA expression was significant on day 21 and was sustained until day 42. The DNA microarray revealed genes significantly increased on day 10, including calgranulin B, solute carrier family 34, thymosin and tubulin, but not fibrogenesis-related cytokines or MMPs/TIMPs. In conclusion, the enhanced gene expression of collagen-I, TGF-β1, CTGF and TIMP-1 and the decreased gene expression of MMP-13 and -2 was noted on day 42 in BDL-induced liver fibrosis.