Mesenchymal stem cells (MSCs) are known to undergo endothelial differentiation in response to treatment with vascular\nendothelial growth factor (VEGF), but their angiogenic ability is poorly characterized. In the present study, we aimed to further\ninvestigate the role of Rho/MRTF-A in angiogenesis by MSCs and the effect of the Rho/MRTF-A pathway on the expression\nof integrins ????1????1 and ????5????1, which are known to mediate physiological and pathological angiogenesis. Our results showed that\nincreased expression of ????1, ????5, and ????1 was observed during angiogenesis of differentiated MSCs, and the Rho/MRTF-A signaling\npathwaywas demonstrated to be involved in regulating the expression of integrins ????1, ????5, and ????1. Luciferase reporter assay andChIP\nassay determined that MRTF-A could bind to and transactivate the integrin ????1 and ????5 promoters. Treatment with the Rho inhibitor\nC3 transferase, the Rho-associated protein kinase (ROCK) inhibitor Y27632 or with shMRTF-A inhibited both the upregulation\nof ????1, ????5, and ????1 as well as angiogenesis. Furthermore, in human umbilical vein endothelial cells (HUVECs), MRTF-A deletion\nled to marked reductions in cell migration and vessel network formation compared with the control. These data demonstrate\nthat Rho/MRTF-A signaling is an important mediator that controls integrin gene expression during MSC-mediated angiogenic\nprocesses.
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