EXPRESSION OF TYPE-IV PROCOLLAGEN AND PROLYL 4-HYDROXYLASE MESSENGER-RNA IN CARBON TETRACHLORIDE-INDUCED LIVER FIBROSIS STUDIED BY INSITU HYBRIDIZATION

An experimental model of liver fibrosis was used to study the expression of type IV procollagen and prolyl 4-hydroxylase mRNAs by in situ hybridization. Paraffin sections of rat liver tissue were examined using non-radioactive digoxigenin-labeled cDNA probes and in situ hybridization employing mouse alpha-1 (IV) procollagen cDNA and chicken prolyl 4-hydroxylase beta-subunit cDNA in order to identify cells responsible for the production of type IV procollagen and prolyl 4-hydroxylase mRNAs after administration of carbon tetrachloride (CCl4). Localization of type IV procollagen and prolyl 4-hydroxylase mRNAs was demonstrated in the cytoplasm of mesenchymal cells after six weeks of CCl4 administration. Type IV procollagen and prolyl 4-hydroxylase mRNAs were noted in hepatocytes after eight and ten weeks respectively. The expression of type IV procollagen mRNA was found in a large number of hepatocytes in proportion to the extent of fibrosis. These results suggest that in addition to the mesenchymal cells, hepatocytes also play an important role in fibrogenesis of the liver.