The FGF system has a key role in regulating vascular integrity
The FGF system has a key role in regulating vascular integrity
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DOI：
10.1172/jci35298
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发表时间：
2008-10-01
影响因子：
15.9
通讯作者：
Simons, Michael
中科院分区：
文献类型：
--
作者：
Murakami, Masahiro;Nguyen, Loc T.;Simons, Michael
内皮细胞单层的完整性对血管稳态和内皮细胞通透性的主动调节至关重要。FGF系统在多种生理和病理条件下发挥重要作用;然而，其在成人血管系统中的作用尚未确定。为了评估FGF系统在成人内皮细胞单层中的作用，我们使用可溶性FGF陷阱或所有FGF受体的显性抑制剂在体外破坏牛主动脉内皮细胞和人隐静脉内皮细胞以及在体内破坏成年小鼠和大鼠内皮细胞中的FGF信号传导。使用这些方法抑制FGF信号传导导致VE-钙粘蛋白/p120-连环蛋白复合物的解离以及粘附蛋白和紧密连接的分解，其进展为内皮细胞的损失、内皮屏障功能的严重损害以及最终的脉管系统的解体。因此，FGF信号传导在维持血管完整性中起关键作用。
The integrity of the endothelial monolayer is essential to blood vessel homeostasis and active regulation of endothelial permeability. The FGF system plays important roles in a wide variety of physiologic and pathologic conditions; however, its role in the adult vasculature has not been defined. To assess the role of the FGF system in the adult endothelial monolayer, we disrupted FGF signaling in bovine aortic endothelial cells and human saphenous vein endothelial cells in vitro and in adult mouse and rat endothelial cells in vivo using soluble FGF traps or a dominant inhibitor of all FGF receptors. The inhibition of FGF signaling using these approaches resulted in dissociation of the VE-cadherin/p120-catenin complex and disassembly of adherens and tight junctions, which progressed to loss of endothelial cells, severe impairment of the endothelial barrier function, and finally, disintegration of the vasculature. Thus, FGF signaling plays a key role in the maintenance of vascular integrity.