The response of endothelial cells (ECs) to a polyurethane (PU) characteristic of surface micelles (similar to 89 nm in diameter) and two novel nanocomposites (PU-Au) and (PU-Ag) containing smaller surface micelles (similar to 14-22 nm in diameter) was investigated. The molecular mechanism by which ECs reacted to nanometric surface micelles was examined. On PU-Au and PU-Ag, cell migration rate was promoted. This was accompanied by the upregulation of endothelial nitric oxide synthase (eNOS) and phosphorylated-Akt (p-Akt) expression. The induced eNOS and p-Akt expression was inhibited by LY294002, indicating that the effect of nanocomposites could be attributed to the PI3K pathway. An elevation of intracellular calcium concentration was noted. Additionally, more actin fibers were induced by PU-Au and PU-Ag. Reduction of actin expression upon addition of Y-27632 (an inhibitor of Rho-GTPase) and SU-1498 (an inhibitor of VEGF-R2) was observed. It was concluded that the nanometric micelles on PU surface may interact with ECs and accelerate their migration by increasing cytoplasmic Ca2+ and stimulating the PI3K/Akt/eNOS signaling pathway.
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