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Dimethylnitrosamine (DMN)-induced liver fibrosis was used as an experimental model to study the relationship between serum concentrations of the N-terminal propeptide of type III procollagen [S-Pro(III)-N-P] and the N-terminal (S-7S) and C-terminal (S-NC1) domains of type IV collagen and hepatic concentrations of type III and IV collagen mRNAs. Increases in S-Pro(III)-N-P, and especially in the two type IV collagen-related antigens, were found to be early events in the formation of DMN-induced hepatic fibrosis. The mean concentration of S-Pro(III)-N-P was 120% of the control mean on day 7 of DMN treatment, 230% on day 14 and 250% on day 21. The corresponding values for S-7S were 260, 950 and 1100% and, for S-NC1, 310, 820 and 1000%. All these changes were very similar to those found in the hepatic concentrations of the respective mRNAs. These data support a previous suggestion that an enhanced production of basement-membrane (type IV) collagen is an early event in the development of the DMN-induced hepatic fibrosis. The results also indicate that S-7S and S-NC1 are very sensitive indicators of changes in type IV collagen metabolism. Data obtained in gel-filtration experiments for these three serum antigens were consistent with the suggestion that all three antigens are mainly derived from the synthesis of the respective collagens.

biochemical journal

Serum concentrations of the <i>N</i>-terminal propeptide of type III procollagen and two type IV collagen fragments and gene expression of the respective collagen types in liver in rats with dimethylnitrosamine-induced hepatic fibrosis

Serum concentrations of the N-terminal propeptide of type III procollagen and two type IV collagen fragments and gene expression of the respective collagen types in liver in rats with dimethylnitrosamine-induced hepatic fibrosis