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Integrin-mediated regulation of vascular smooth muscle cells

整合素介导的血管平滑肌细胞调节

基本信息

批准号：
11694307
负责人：
KOYAMA Hidenori
金额：
$ 1.98万
依托单位：
Osaka City University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B).
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2000
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-11694307/
关键词：
extracellular matrix thrombospondin alpha v beta 3 integrin atherosclerosis gene expression actinin arterial balloon injury αvβ_3インテグリンフィブロネクチン細胞遊走 Subtraction cloning

项目摘要

Proliferation and αvβ3 integrin-dependent cell migration of vascular smooth muscle cells are suppressed on polymerized type I collagen. To identify genes specifically regulated in human smooth muscle cells by polymerized collagen, we used the suppressive subtraction hybridization technique. As compared with smooth muscle cells cultured on monomer collagen, polymerized collagen suppresses : 1. a number of other extracellular matrix proteins, including fibronectin, thrombospondin-1, tenascin-C, and cysteine-rich protein 61 ; 2. actin-binding proteins including α-actinin ; 3. signaling molecules ; 4. protein synthesis-associated proteins ; and 5. genes with unknown functions. Some of the identified genes, including cysteine-rich protein 61, show unique kinetics of mRNA regulation by monomer or polymerized collagen distinct from growth factors, suggesting extracellular matrix-specific gene modulation. Moreover, in vivo balloon catheter-mediated injury to the rat carotid artery induces many of the genes that are suppressed by polymerized collagen. Protein levels of thrombospondin-1 and fibronectin are also suppressed by polymerized collagen. Thrombospondin-1-mediated SMC migration on vitronectin is significantly inhibited after culture on polymerized collagen for 24 hours, which is associated with decreased α-actinin accumulation at focal adhesions. Thus, polymerized type I collagen dynamically regulates gene expression, pericellular accumulation of extracellular matrix molecules, and the response to a given matrix molecule.

血管平滑肌细胞的增殖和αvβ3整合素依赖性细胞迁移在聚合的I型胶原上受到抑制。为了鉴定聚合胶原在人平滑肌细胞中特异性调控的基因，我们使用了抑制性消减杂交技术。与在单体胶原上培养的平滑肌细胞相比，聚合胶原抑制：1。许多其他细胞外基质蛋白，包括纤连蛋白、血小板反应蛋白-1、腱生蛋白-C和富含半胱氨酸的蛋白61 ; 2.肌动蛋白结合蛋白，包括α-肌动蛋白; 3.信号分子; 4.蛋白质合成相关蛋白质;和5.功能未知的基因一些已鉴定的基因，包括富含半胱氨酸的蛋白61，显示出独特的动力学的mRNA调控单体或聚合的胶原蛋白不同的生长因子，这表明细胞外基质特异性基因的调制。此外，体内球囊导管介导的大鼠颈动脉损伤诱导了许多被聚合胶原抑制的基因。血小板反应蛋白-1和纤连蛋白的蛋白水平也受到聚合胶原的抑制。在聚合胶原上培养24小时后，血小板反应蛋白-1介导的SMC在玻连蛋白上的迁移被显著抑制，这与粘连灶处α-辅肌动蛋白积聚减少有关。因此，聚合的I型胶原动态调节基因表达、细胞外基质分子的细胞周积累以及对给定基质分子的反应。