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

肝纤维化过程中胶原表达与合成和降解速率相关的研究

基本信息

批准号：
06670559
负责人：
SHIMIZU Ichiro
金额：
$ 1.41万
依托单位：
University of Tokushima
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1994
资助国家：
日本
起止时间：
1994 至 1995
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-06670559/
关键词：
Collagen Hepatic fibrosis Gene expression Dimethylnitrosamine Collagenase Collagenase inhibitor Pig serum

项目摘要

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.

胶原沉积的量必须取决于合成和降解速率之间的平衡。本研究旨在观察二甲基亚硝胺（DMN）诱导大鼠肝纤维化过程中Ⅰ、Ⅲ型前胶原、金属蛋白酶-1（MMP-1）和金属蛋白酶组织抑制因子-1（TIMP-1）的基因表达，Ⅰ、Ⅲ型胶原的免疫定位，以及肝胶原含量的变化。而PS诱导的纤维化显示I型胶原基因表达和免疫沉积的优势。DMN治疗后第14天和PS治疗后第10周，纤维化最严重，III型前胶原基因表达最高，此时III型胶原免疫沉积占主导地位。DMN剂量依赖性地增加肝胶原含量;第14天III型前胶原mRNA水平增加。相对MMP-1 mRNA水平增加早期肝纤维化和低DMN剂量的第14天。高剂量DMN降低MMP-1 mRNA水平，增加胶原含量，导致肝纤维化。因此，纤维化肝胶原含量可能首先显著增加，部分原因是I型胶原和MMP-1表达率之间的平衡，并且I型或III型胶原表达可能根据发病情况在胶原积累中起作用。