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.
Savolainen
E R
ER
Collagen Research Unit, University of Oulu, Finland.
Brocks
D
D
Ala-Kokko
L
L
Kivirikko
K I
KI
D000818:Animals; D002850:Chromatography, Gel; D003094:Collagen / Q000096:biosynthesis / Q000097:blood* / Q000235:genetics; D004128:Dimethylnitrosamine; D005260:Female; D008099:Liver / Q000378:metabolism*; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism*; D010446:Peptide Fragments / Q000097:blood* / Q000235:genetics; D011347:Procollagen / Q000097:blood* / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D011863:Radioimmunoassay; D051381:Rats; D011919:Rats, Inbred Strains
D010446:Peptide Fragments; D011347:Procollagen; D012333:RNA, Messenger; C041876:procollagen Type III-N-terminal peptide; D003094:Collagen; D004128:Dimethylnitrosamine