Fukui R, Shibata N, Kohbayashi E, Amakawa M, Furutama D, Hoshiga M, Negoro N, Nakakouji T, Ii M, Ishihara T, Ohsawa N
First Department of Internal Medicine, Osaka Medical College, Takatsuki-city, Japan.
Atherosclerosis. 1997 Jul 11;132(1):53-9. doi: 10.1016/s0021-9150(97)00086-5.
In vascular smooth muscle cells (SMCs), proliferation and migration contribute to lesion formation after arterial injury. In the cell cycle, several cyclin-dependent kinases (cdks) inhibitors are implicated in the regulating of cyclin-cdk activity such as p21Cip1, p16Ink4 and p27Kip1. Although Cip1 inhibits SMC proliferation, its effects on SMC migration are unknown. To test the hypothesis that Cip1 inhibits SMCs migration and proliferation, we transfected the Cip1 gene into a strain of rabbit aortic SMCs (SM3 cells). Both the spreading and the attachment of Cip1-transfected SM3 cells to extracellular matrices (ECMs) were inhibited compared to that of vector-transfected cells. In the modified Boyden's chamber assay the effect of fibronectin on the migratory activity of Cip1-transfected SM3 cells was significantly less than that of vector transfected cells in response to PDGF-BB. These data suggested that Cip1 inhibited both the migration and proliferation of SMC.
在血管平滑肌细胞(SMC)中,增殖和迁移有助于动脉损伤后病变的形成。在细胞周期中,几种细胞周期蛋白依赖性激酶(cdk)抑制剂参与调节细胞周期蛋白-cdk活性,如p21Cip1、p16Ink4和p27Kip1。虽然Cip1抑制SMC增殖,但其对SMC迁移的影响尚不清楚。为了验证Cip1抑制SMC迁移和增殖的假说,我们将Cip1基因转染到一株兔主动脉SMC(SM3细胞)中。与载体转染细胞相比,Cip1转染的SM3细胞向细胞外基质(ECM)的铺展和附着均受到抑制。在改良的博伊登室试验中,在血小板衍生生长因子-BB(PDGF-BB)刺激下,纤连蛋白对Cip1转染的SM3细胞迁移活性的影响明显小于载体转染细胞。这些数据表明,Cip1抑制SMC的迁移和增殖。