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The age-related alterations of the expression of type I collagen and collagen-binding heat shock protein

I 型胶原和胶原结合热休克蛋白表达的年龄相关变化

基本信息

批准号：
04836008
负责人：
SAGA Shinsuke
金额：
$ 1.15万
依托单位：
Nagoya University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1992
资助国家：
日本
起止时间：
1992 至 1993
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-04836008/
关键词：
aging stress protein collagen-binding HSP47 fibroblasts heat-response procollagens molecular chaperone 熱ショック蛋白質

项目摘要

Collagen-binding heat shock protein of molecular weight 47,000(HSP47)is a resident protein in the endoplasmic reticulum(ER), and assumed to play a specific role on the processing of procollagen molecules, as a molecular chaperon specific for procollagen molecules. In this study, we investigated the age-related alteration of the heat response of HSP47 expression in cultured murine and human fibroblasts. In the cells in low population doubling level(PDL), HSP47 expression was more inducible by heat treatment in those derived from young mice and persons than from old ones. On the other hand, the cells in high PDL showed very low heat response of HSP47 expression regardless of the age of donors. Northern blot analysis of HSP47m-RNA indicated that the age related attenuation of HSP47 expression was regulated by transcriprional mechanisms. Furthemore, immunofluorescent analysis using a monoclonal antibody against amino-terminal propeptide of type I procollagen revealed that much more procollagen molecules retained in ER lumen of the cells from old persons than in the cells from young persons. The retention of procollagen molecules in ER was much more prominent in heat-treated cells, indicating the possibility that the decrease of heat response of HSP47 in the cells from old persons can explain the retention of procollagen molecules in ER lumen.

分子量为47000的胶原结合热休克蛋白（HSP47）是内质网（ER）中的一种驻留蛋白，被认为是前胶原分子特异性的分子伴侣，在前胶原分子的加工过程中起着特定的作用。在这项研究中，我们研究了HSP47在培养的小鼠和人成纤维细胞中表达的热反应的年龄相关变化。在低群体倍增水平（PDL）的细胞中，热处理对来自幼鼠和人的细胞的HSP47表达的诱导作用强于来自老年小鼠的细胞。另一方面，无论供体年龄如何，高PDL的细胞对HSP47表达的热反应都很低。HSP47m-RNA的Northern blot分析表明，HSP47表达的年龄相关性衰减受转录机制的调控。此外，利用针对I型前胶原氨基末端前肽的单克隆抗体进行免疫荧光分析显示，老年人细胞内质网腔中保留的前胶原分子比年轻人细胞中保留的多。内质网中前胶原分子的滞留在热处理细胞中更为突出，说明老年人细胞中HSP47热反应的降低可能可以解释内质网腔中前胶原分子的滞留。