Rho/MRTF-A-Induced Integrin Expression Regulates Angiogenesis in Differentiated Multipotent Mesenchymal Stem Cells.
Rho/MRTF-A-Induced Integrin Expression Regulates Angiogenesis in Differentiated Multipotent Mesenchymal Stem Cells.
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Rho/MRTF-A 诱导的整合素表达调节分化多能间充质干细胞中的血管生成
DOI：
10.1155/2015/534758
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发表时间：
2015
影响因子：
4.3
通讯作者：
Zhang TC
中科院分区：
文献类型：
--
作者：
Zhang R;Wang N;Zhang M;Zhang LN;Guo ZX;Luo XG;Zhou H;He HP;Zhang TC
已知间充质干细胞(MSCs)在血管内皮生长因子(VEGF)的作用下会发生内皮细胞分化，但其血管生成能力的特征较差。本研究旨在进一步研究Rho/mrtf-A在骨髓间充质干细胞血管生成中的作用，以及Rho/mrtf-A通路对α1β1和α5β1的表达的影响，这两种整合素介导生理性和病理性血管生成。结果表明，在分化的骨髓间充质干细胞血管生成过程中，α-1、α-5和β-1的表达增加，Rho/α-A信号通路参与了整合素α-1、β-5和α-1的表达调控。荧光素酶报告基因分析和芯片检测表明，α-A可以与整合素MSC-1和MRS-5启动子结合并反式激活。用Rho抑制剂C3转移酶、Rho相关蛋白激酶(ROCK)抑制剂Y27632或shMRTF-A处理均可抑制α-1、α-5和β-1的表达以及血管生成。此外，在人脐静脉内皮细胞(HUVECs)中，MRTF-A缺失导致细胞迁移和血管网络形成明显减少。这些数据表明，在MSC介导的血管生成过程中，Rho/MRTF-A信号是控制整合素基因表达的重要介质。
Mesenchymal stem cells (MSCs) are known to undergo endothelial differentiation in response to treatment with vascular endothelial growth factor (VEGF), but their angiogenic ability is poorly characterized. In the present study, we aimed to further investigate the role of Rho/MRTF-A in angiogenesis by MSCs and the effect of the Rho/MRTF-A pathway on the expression of integrins α1β1 and α5β1, which are known to mediate physiological and pathological angiogenesis. Our results showed that increased expression of α1, α5, and β1 was observed during angiogenesis of differentiated MSCs, and the Rho/MRTF-A signaling pathway was demonstrated to be involved in regulating the expression of integrins α1, α5, and β1. Luciferase reporter assay and ChIP assay determined that MRTF-A could bind to and transactivate the integrin α1 and α5 promoters. Treatment with the Rho inhibitor C3 transferase, the Rho-associated protein kinase (ROCK) inhibitor Y27632 or with shMRTF-A inhibited both the upregulation of α1, α5, and β1 as well as angiogenesis. Furthermore, in human umbilical vein endothelial cells (HUVECs), MRTF-A deletion led to marked reductions in cell migration and vessel network formation compared with the control. These data demonstrate that Rho/MRTF-A signaling is an important mediator that controls integrin gene expression during MSC-mediated angiogenic processes.
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影响因子：
4.8
作者：
Bryan, Brad A.;Dennstedt, Emily;D'Amore, Patricia A.
通讯作者：
D'Amore, Patricia A.
影响因子：
15.9
作者：
Weinl, Christine;Riehle, Heidemarie;Nordheim, Alfred
通讯作者：
Nordheim, Alfred
DOI：
10.1073/pnas.1220185110
发表时间：
2013-02-19
影响因子：
11.1
作者：
Gomes, Samirah A.;Rangel, Erika B.;Hare, Joshua M.
通讯作者：
Hare, Joshua M.
影响因子：
5.2
作者：
Oswald, J;Boxberger, S;Werner, C
通讯作者：
Werner, C
血管内皮生长因子通过 Rho/心肌素相关转录因子 A 信号通路刺激间充质干细胞向内皮分化
DOI：
10.1016/j.biocel.2013.04.021
发表时间：
2013-07-01
影响因子：
4
作者：
Wang, Nan;Zhang, Rui;Zhang, Tong-Cun
通讯作者：
Zhang, Tong-Cun