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.
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.