Mechanical stress-activated PKCδ regulates smooth muscle cell migration

Vascular smooth muscle cells (SMCs) are exposed to altered mechanical stress that may contribute to SMC migration in the development of atherosclerosis. Signal transduction pathways in SMCs activated by mechanical stress that instigate cell migration are undefined. Herein, we provide evidence that mechanical stress enhances SMC migration, which is mediated, at least in part, by protein kinase C (PKC) δ. When rat SMCs cultivated on a flexible membrane were subjected to cyclic strain stress (60 cycles/min, 5, 15, or 20% elongation), PKCδ was translocated to the Triton-insoluble fraction, whereas PKCα was translocated to the membrane, which was confirmed by PKC kinase assays. Immunofluorescence and actin staining revealed a cytoskeleton translocation of PKCδ in SMCs stimulated by cyclic strain. PKCδ-deficient SMCs cultivated from PKCδ−/− mice showed an abnormal cytoskeleton structure, which was related to a diminished phosphorylation of paxillin, focal adhesion kinase, and vinculin in response to mechanical stress. Mechanical stress enhanced SMC migration, which was diminished in PKCδ−/− SMCs. Taken together, our data demonstrated that mechanical stress activates PKCδ translocation to the cytoskeleton, which is related to decreased SMC migration and indicates that PKCδ is a key signal transducer between mechanical stress and cell migration.