FGD5 Mediates Proangiogenic Action of Vascular Endothelial Growth Factor in Human Vascular Endothelial Cells
FGD5 Mediates Proangiogenic Action of Vascular Endothelial Growth Factor in Human Vascular Endothelial Cells
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DOI：
10.1161/atvbaha.111.244004
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发表时间：
2012-04-01
影响因子：
8.7
通讯作者：
Rikitake, Yoshiyuki
中科院分区：
文献类型：
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作者：
Kurogane, Yusuke;Miyata, Muneaki;Rikitake, Yoshiyuki
目的-血管内皮生长因子 (VEGF) 发挥促血管生成作用并诱导多种促血管生成信号通路的激活，包括 Rho 家族小 G 蛋白。然而，人们对血管内皮细胞 (EC) 中 Rho 家族小 G 蛋白的调节因子知之甚少。在这里，我们试图阐明鸟嘌呤核苷酸交换因子 FGD 家族成员 FGD5 的表达、亚细胞定位、下游效应子和促血管生成作用。方法和结果-FGD5 在培养的人血管 EC 中选择性表达。免疫荧光显微镜显示，在人脐静脉 EC 的外周膜皱褶和核周区域观察到 FGD5 信号。 FGD5 的过表达增加了 Cdc42 活性，而小干扰 RNA 敲低 FGD5 则抑制了 VEGF 诱导的 Cdc42 和细胞外信号调节激酶的激活。 FGD5 的敲低可减弱 VEGF 促进的人脐静脉 EC 的毛细血管样网络形成、通透性、定向运动和增殖以及定向细胞运动过程中高尔基复合体的重新定向。结论 - 这项研究首次证明了 FGD5 在血管 EC 中的表达、亚细胞定位和功能。结果表明，FGD5 调节血管内皮细胞中 VEGF 的促血管生成作用，包括网络形成、通透性、定向运动和增殖。 （动脉硬化血栓 Vasc Biol.2012；32：988-996。）
Objective-Vascular endothelial growth factor (VEGF) exerts proangiogenic action and induces activation of a variety of proangiogenic signaling pathways, including the Rho family small G proteins. However, regulators of the Rho family small G proteins in vascular endothelial cells (ECs) are poorly understood. Here we attempted to clarify the expression, subcellular localization, downstream effectors, and proangiogenic role of FGD5, a member of the FGD family of guanine nucleotide exchange factors.Methods and Results-FGD5 was shown to be selectively expressed in cultured human vascular ECs. Immunofluorescence microscopy showed that the signal for FGD5 was observed at peripheral membrane ruffles and perinuclear regions in human umbilical vein ECs. Overexpression of FGD5 increased Cdc42 activity, whereas knockdown of FGD5 by small interfering RNAs inhibited the VEGF-induced activation of Cdc42 and extracellular signal-regulated kinase. VEGF-promoted capillary-like network formation, permeability, directional movement, and proliferation of human umbilical vein ECs and the reorientation of the Golgi complex during directional cell movement were attenuated by knockdown of FGD5.Conclusion-This study provides the first demonstration of expression, subcellular localization, and function of FGD5 in vascular ECs. The results suggest that FGD5 regulates proangiogenic action of VEGF in vascular ECs, including network formation, permeability, directional movement, and proliferation. (Arterioscler Thromb Vasc Biol. 2012; 32: 988-996.)