Integrin-mediated regulation of vascular smooth muscle cells

聚合的I型胶原抑制血管平滑肌细胞的增殖和αvβ3整合素依赖的细胞迁移。为了确定聚合的胶原蛋白在人的血管平滑肌细胞中的特异性调控基因，我们使用了抑制消减杂交技术。与在单体胶原上培养的平滑肌细胞相比，聚合的胶原抑制：1.其他一些细胞外基质蛋白，包括纤维连接蛋白、血栓反应蛋白-1、肌腱蛋白-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；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，表现出与生长因子不同的单体或聚合胶原对mRNA调控的独特动力学，表明细胞外基质特异的基因调控。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的胶原蛋白抑制的基因。凝血酶原蛋白-1和纤维连接蛋白的蛋白水平也被聚合的胶原蛋白抑制。在聚合胶原上培养24小时后，凝血酶敏感蛋白-1介导的SMC在玻璃体连结蛋白上的迁移受到显著抑制，这与局部粘连处α-Actinin积聚减少有关。因此，聚合的I型胶原可以动态调节基因表达、细胞外基质分子在细胞周围的积聚，以及对给定基质分子的反应。

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.