Angiopoietin-1 prevents VEGF-induced endothelial permeability by sequestering src through mDia
Angiopoietin-1 prevents VEGF-induced endothelial permeability by sequestering src through mDia
复制标题
DOI：
10.1016/j.devcel.2007.10.019
复制
发表时间：
2008-01-01
影响因子：
11.8
通讯作者：
Gutkind, J. Silvio
中科院分区：
文献类型：
--
作者：
Gavard, Julie;Patel, Vyomesh;Gutkind, J. Silvio
血管内皮生长因子（VEGF）和血管生成素1 （Ang1）都是有效的促血管生成因子，但是，VEGF导致血管通透性，Ang1稳定血管并保护血管免受VEGF诱导的血浆渗漏。Ang1的抗血管通透性机制尚不明确。在这里，我们证明了Ang1阻止了VEGF诱导磷酸化依赖性粘附分子ve -钙粘蛋白重新分布的能力，从而挽救了内皮屏障功能。Ang1抑制VEGF对Src的激活，VEGF是连接VEGF受体与VE-cadherin内化途径的最上游组分。事实上，Ang1通过RhoA促进mDia的激活，从而导致mDia与Src的关联。这最终剥夺了VEGF受体促进内皮细胞-细胞接触和细胞旁通透性破坏所需的基本分子。
Vascular endothelial growth factor (VEGF) and Angiopoietin 1 (Ang1) are both potent proangiogenic factors, but, whereas VEGF causes vascular permeability, Ang1 stabilizes blood vessels and protects them from VEGF-induced plasma leakage. The antivascular permeability mechanisms deployed by Ang1 are still undefined. Here, we demonstrate that Ang1 halts the ability of VEGF to induce the phosphorylation-dependent redistribution of the adhesion molecule VE-cadherin, thereby rescuing the endothelial barrier function. Ang1 inhibits the activation of Src by VEGF, the most upstream component of the pathway linking VEGF receptors to VE-cadherin internalization. Indeed, Ang1 promotes the activation of mDia through RhoA, resulting in the association of mDia with Src. This ultimately deprives VEGF receptors of an essential molecule required for promoting the disruption of endothelial cell-cell contacts and paracellular permeability.