EXPRESSION OF TYPE-I AND TYPE-III COLLAGENS DURING THE COURSE OF DIMETHYLNITROSAMINE-INDUCED HEPATIC-FIBROSIS IN RATS

Aims/Background: We wished to clarify the mechanisms that account for the increase in hepatic collagen accumulation during hepatic fibrosis. Methods. The gene expression of type I and type III procollagens and matrix metalloproteinase-1 (MMP-1) was measured by Northern blot analy sis; immunolocalization of both types of collagen was estimated by ind irect immunohistochemical assay; and the hepatic content of collagen a nd malondialdehyde (MDA), a product of lipid peroxidation, were assaye d in hepatic fibrosis induced in rats with a single dose of dimethylni trosamine (DMN). Results. During the experimental period, more type I procollagen mRNA was found than type III procollagen mRNA. The immunor eactive intensity of type I collagen was greater in necrotic areas nea r central veins 3 days after DMN treatment than it was on day 9, where as the type III collagen immunodeposition for the latter period of the hepatic fibrosis was stronger than it was on day 3. As compared with controls, hepatic collagen content increased significantly after 3 day s and continued, increasing gradually, as did type I and III procollag en mRNA levels. On day 14, fibrosis was greatest and both types of pro collagen gene expression were at their highest, and type I and III pro collagen mRNA levels and hepatic collagen content increased as the dos age of DMN was raised. MMP-1 mRNA levels increased early in hepatic fi brogenesis, and increased on day 14 when DMN dosages were low. Hepatic MDA levels increased rapidly for 3 days after DMN treatment, remainin g significantly higher than control values and showing a significant i ncrease even in response to low DMN doses on day 14. Conclusions: Our results suggested that fibrotic liver collagen content may make its fi rst notable increase due in part to the balance between type I collage n and MMP-1 expression rates. Also, lipid peroxidation may be importan t in the mechanism of hepatofibrogenesis.