Protein Kinase C δ Activated Adhesion Regulates Vascular Smooth Muscle Cell Migration
2007
Background Vascular smooth muscle cell (VSMC) migration, fundamental in the pathophysiology of atherogenesis and restenosis, is a coordinated process governed by the formation and disassembly of focal adhesions. Previous studies have demonstrated that VSMC migration is regulated via a signaling network involving protein kinase C delta (PKCδ). In these studies, we test the hypothesis that PKCδ regulates VSMC migration through modulation of cell adhesion. Materials and methods Using primary VSMCs isolated from PKCδ wild type (+/+) and knock-out (−/−) mice, the effects of PKCδ on VSMC migration and adhesion were assessed by chemotaxis and cell adhesion. Results In evaluating cell migration, we found a decrease in platelet-derived growth factor-BB (PDGF-BB; 5 ng/mL × 6 h) stimulated migration of PKCδ–/–VSMCs as compared to PKCδ+/+VSMCs, by 59.4 ± 5.9% ( P P P P m ), a selective inhibitor of PKCδ, blocked migration and attachment of VSMCs by 56.8 ± 3.4% ( P P Conclusions Taken together, our data indicate that PKCδ activation is necessary for VSMC adhesion, which could, at least in part, contribute to the regulatory function of this kinase in cell migration thus pathogenesis of vascular lesions.
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