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

胶原蛋白的沉积量必须取决于合成和降解速度之间的平衡。本研究的目的是研究二甲基亚硝胺(DMN)诱导的大鼠肝纤维化过程中I型和III型前胶原、基质金属蛋白酶-1(MMP1)及其组织抑制因子-1(TIMP-1)的基因表达，以及I型和III型胶原的免疫定位，以及肝组织胶原含量的变化。在DMN治疗后第14天和PS治疗后10周，纤维化程度最大，III型前胶原基因表达最高，此时III型胶原免疫沉积为主。DMN可剂量依赖性地增加肝脏胶原含量，III型前胶原mRNA水平在第14天升高，肝纤维化早期及低剂量DMN组肝组织中MMP1mRNA相对水平升高，高剂量DMN组MMP1mRNA水平降低，胶原含量增加，导致肝纤维化。因此，纤维化肝脏胶原含量可能首先显著增加，部分原因是I型胶原和基质金属蛋白酶-1表达之间的平衡，根据发病情况，I型或III型胶原表达可能在胶原堆积中发挥作用。

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.