Koyama H, Raines E W, Bornfeldt K E, Roberts J M, Ross R
Department of Pathology, University of Washington, Seattle 98195-7470, USA.
Cell. 1996 Dec 13;87(6):1069-78. doi: 10.1016/s0092-8674(00)81801-2.
Arterial smooth muscle cells (SMCs) are arrested in the G1 phase of the cell cycle on polymerized type I collagen fibrils, while monomer collagen supports SMC proliferation. Cyclin E-associated kinase and cyclin-dependent kinase 2 (cdk2) phosphorylation are inhibited on polymerized collagen, and levels of the cdk2 inhibitors p27Kip1 and p21Cip1/Waf1 are increased compared with SMCs on monomer collagen. p27Kip1 associates with the cyclin E-cdk2-p21Cip1/Waf1 complex in SMCs on polymerized collagen. Monovalent blocking antibodies to alpha2 integrins, integrins that mediate adhesion to both forms of collagen, mimic these effects on monomer collagen. Furthermore, polymerized collagen rapidly suppresses p70 S6 kinase, a possible regulator of p27Kip1. Thus, fibrillar collagen specifically regulates early integrin signaling that may lead to up-regulation of cdk2 inhibitors and inhibition of SMC proliferation.
动脉平滑肌细胞（SMC）在聚合的I型胶原纤维上停滞于细胞周期的G1期，而单体胶原则支持SMC增殖。在聚合胶原上，细胞周期蛋白E相关激酶和细胞周期蛋白依赖性激酶2（cdk2）的磷酸化受到抑制，与单体胶原上的SMC相比，cdk2抑制剂p27Kip1和p21Cip1/Waf1的水平升高。在聚合胶原上的SMC中，p27Kip1与细胞周期蛋白E-cdk2-p21Cip1/Waf1复合物相关联。针对α2整合素的单价阻断抗体（介导与两种形式胶原黏附的整合素）在单体胶原上模拟了这些效应。此外，聚合胶原迅速抑制p70 S6激酶，这可能是p27Kip1的一种调节因子。因此，纤维状胶原特异性调节早期整合素信号传导，这可能导致cdk2抑制剂上调并抑制SMC增殖。
