钙网蛋白基因缺陷细胞中MMP2和MMP9的表达及其调节机制

发布时间：2018-10-23 14:27

【摘要】：简介: 钙网蛋白(Calreticulin,crt)是一种近年来备受瞩目的、影响心脏发育的重要的调节蛋白。它由Ostwald在1974年首次从细胞中分离出来,是一种存在于非肌细胞内质网上的主要钙结合蛋白。钙网蛋白的功能包括(1)分子伴侣: 指导新合成蛋白的折叠;(2)调节细胞粘附,(3)调节钙离子的代谢。钙网蛋白基因敲除的小鼠(crt-/-)可导致胚胎小鼠胎死宫内,其直接死因是小鼠心脏发育障碍及脐疝形成。这些改变主要是因为细胞外基质蛋白含量改变所致。基质金属蛋白酶(matrix metalloproteinases,MMPs)是一组能降解细胞外基质锌依赖酶,在多种心血管疾病如动脉瘤、心室重构、心脏损伤以及再狭窄等病理生理过程中发挥重要作用。其中MMP2及MMP9可引起内皮细胞及平滑肌细胞的增生及迁移,从而导致血管形成。其活性的变化可影响到血管的形成及心脏的发育;然而,crt-/-小鼠心脏发育不全的原因是否与MMP2和MMP9的活性变化有关尚不清楚。本工作从mRNA→蛋白→蛋白活性等方面以论证crt-/- 影响心脏发育的途径,提供新的机制。方法: 野生型(wt)和基因缺陷型小鼠(crt-/-)的胚胎成纤维细胞(mouse
[Abstract]:Introduction: calmodulin (Calreticulin,crt) is an important regulatory protein that affects cardiac development in recent years. It was first isolated from cells by Ostwald in 1974 and is a major calcium-binding protein present in the endoplasmic reticulum of non-myocytes. The functions of calmodulin include: (1) molecular chaperone: to direct the folding of newly synthesized proteins; (2) to regulate cell adhesion; (3) to regulate the metabolism of calcium ions. Mice with calcium reticulum egg white gene knockout (crt-/-) can cause fetal mice to die in the womb. The direct cause of death was cardiac dysgenesis and umbilical hernia formation in mice. These changes are mainly due to changes in extracellular matrix protein content. Matrix metalloproteinases (matrix metalloproteinases,MMPs) are a group of zinc-dependent enzymes that can degrade extracellular matrix. It plays an important role in many cardiovascular diseases such as aneurysm, ventricular remodeling, heart injury and restenosis. MMP2 and MMP9 can induce proliferation and migration of endothelial cells and smooth muscle cells, which lead to angiogenesis. The changes of its activity may affect the formation of blood vessels and the development of heart. However, it is not clear whether the cause of cardiac hypoplasia in crt-/- mice is related to the alteration of MMP2 and MMP9 activity. In order to demonstrate the pathway of crt-/- affecting cardiac development from the aspects of mRNA protein activity, this work provides a new mechanism. Methods: embryonic fibroblasts (mouse) from wild-type (wt) and gene-deficient mice (crt-/-)
【学位授予单位】：汕头大学
【学位级别】：博士
【学位授予年份】：2005
【分类号】：R363

【相似文献】