权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Roles of endothelin-1 in normal and fibrotic rat livers

内皮素-1 在正常和纤维化大鼠肝脏中的作用

基本信息

批准号：
10670036
负责人：
DOI Yoshiaki
金额：
$ 1.02万
依托单位：
University of Occupational and Environmental Health
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 1999
项目状态：
已结题

项目摘要

Immunocytochemical localization of big endothelin-1 (big ET-1), ET-1 and ET receptor A and B (ETィイD2AィエD2 and ETィイD2BィエD2), and gene expression of preproET-1 mRNA were examined on the rat liver vasculature. Immunoreactivities for big ET-1 and for ET-1 were preferentially seen along the endothelium of inter16bular veins (IV). Expression of preproET-1 mRNA was detected in the endothelium. Immunoelectron microscopy showed that rough endoplasmic cisterns were immunoreactive for big ET-1, while Weibel-Palade bodies, a storage site for ET-1, were immunoreactive for ET-1 in endothelial cells of IV. The plasma membrane of hepatic stellate cells (HSCs) was immunoreactive for both ETィイD2AィエD2 and ETィイD2BィエD2 receptor antibodies. These findings suggest that endothelial cells of IV are the major site of synthesis of ET-1, and that ET-1 receptor-mediated HSC contraction is involved in the regulation of hepatic sinusoidal blood flow as previously cited in mammalian liver cirrhosis. We also examined immunocytochemical localizations of big ET-1 and ET-1 on fibrotic livers of the thioacetamide-treated rats. Immunoreactivities for big ET-1 and for ET-1 were preferentially seen in HSCs which exhibit characteristics of myofibroblasts. Immunoelectron microscopy showed that rough endoplasmic cisterns of the HSCs Were immunoreactive for big ET-1. Since it was already reported by several biochemists that ET-1 accelerates the synthetic ability of collagen fibers in HSCs, these results indicate that ET-1, synthesized in HSCs, is involved in the progress of liver fibrosis in an autocrine fashon.

用免疫细胞化学方法检测大鼠肝血管大内皮素-1(BIG ET-1)、ET-1及ET受体A、B(ETィイD2aィエD2和ETィイD2BィエD2)的免疫细胞化学定位及前ProET-1mRNA的基因表达。大的ET-1和ET-1的免疫反应主要见于肾小管间静脉(IV)的内皮细胞。内皮细胞表达前ProET-1mRNA。免疫电子显微镜显示，粗面内质池表达大ET-1，而IV型肝内皮细胞表达ET-1。肝星状细胞质膜表达ET-ィイD2aィエD2和ETィイD2BィエD2受体抗体。这些结果表明，IV型内皮细胞是合成ET-1的主要部位，而ET-1受体介导的HSC收缩参与了哺乳动物肝硬变时肝窦血流的调节。我们还检测了大ET-1和ET-1在硫代乙酰胺处理的大鼠肝纤维化中的免疫细胞化学定位。HSCs主要表达BIG和ET-1，具有肌成纤维细胞的特征。免疫电子显微镜显示HSCs的粗面内质池大ET-1免疫反应阳性。由于已有多位生物化学家报道ET-1可促进HSCs合成胶原纤维的能力，这些结果表明，HSCs合成的ET-1参与了肝纤维化的自分泌过程。