LOCALIZATION OF TYPE-III PROCOLLAGEN AND PROLYL 4-HYDROXYLASE MESSENGER-RNAS IN FIBROTIC HUMAN LIVER

The increased collagen production in liver fibrosis is accompanied by many changes in the biosynthetic pathway, such as an increase in the transcription of procollagen mRNA and the activities of the post-translational enzymes. Prolyl 4-hydroxylase is a key enzyme in collagen biosynthesis, which stabilizes triple-helical conformation of procollagen. So, procollagen and prolyl 4-hydroxylase mRNAs are needed for mature collagen synthesis. In this study, the localization of type III procollagen and prolyl 4-hydroxylase mRNAs in fibrotic human liver was detected by in situ hybridization. Frozen and deparaffinized sections of human liver were examined using non-radioactive digoxigenin-labeled cDNA probes. Type III procollagen and prolyl 4-hydroxylase mRNAs were found to be localized not only in the cytoplasm of mesenchymal cells but also in hepatocytes. Furthermore, using serial sections, both mRNAs were found to be present in the same hepatocytes. These results suggest that hepatocytes produce triple-helical procollagen chains and promote liver fibrogenesis along with mesenchymal cells.