Study on the collagen expression related with the rates of synthesis and degradation during the course of hepatic fibrosis

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The amount of collagen deposited must depend on the balance between the rates of synthesis and degradation. Our objectives were to study the gene expression of type I and III procollagens, metalloproteinase-1 (MMP-1) and tissue inhibitor of metalloproteinase-1 (TIMP-1), to determine type I and III collagen immunolocalization, and to assay hepatic collagen content during the course of hepatic fibrosis induced in rats by administration of dimethylnitrosamine (DMN), whereas PS-induced fibrosis showed the preponderance of type I collagen gene expression and immunodeposition. Fibrosis was greatest and type III procollagen gene expression highest on day 14 after DMN treatment and 10 weeks after PS treatment, when type III collagen immunodeposition predominated. DMN increased hepatic collagen contents dose-dependently ; type III procollagen mRNA levels increased on day 14. Relative MMP-1 mRNA levels increased early in hepatic fibrogenesis and with low DMN dosages on day 14. Decreased MMP-1 mRNA levels with high DMN dosages increased collagen content and caused hepatic fibrosis. Fibrotic liver collagen content may thus first notably increase partly due to the balance between type I collagen and MMP-1 expression retes, and type I or III collagen expression may play a role in collagen accumulation according as pathogenetic circumstances.