INHIBITION OF SMOOTH-MUSCLE CELL-MIGRATION BY THE P21 CYCLIN-DEPENDENT KINASE INHIBITOR (CIP1)

In vascular smooth muscle cells (SMCs), proliferation and migration co ntribute 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 p21(Cip1), p16(Ink4) and p27(Kip1). Although Cipl inhibits SMC proliferation, its effects on S MC migration are unknown. To test the hypothesis that Cip1 inhibits SM Cs migration and proliferation, we transfected the Cip1 gene into a st rain of rabbit aortic SMCs (SM3 cells). Both the spreading and the att achment of Cip1-transfected SM3 cells to extracellular matrices (ECMs) were inhibited compared to that of vector-transfected cells. In the m odified Boyden's chamber assay the effect of fibronectin on the migrat ory activity of Cip1-transfected SM3 cells was significantly less than that of vector transfected cells in response to PDGF-BB. These data s uggested that Cipl inhibited both the migration and proliferation of S MC. (C) 1997 Elsevier Science Ireland Ltd.