Regulation of vasculogenesis and angiogenesis by EphB/ephrin-B2 signaling between endothelial cells and surrounding mesenchymal cells
Regulation of vasculogenesis and angiogenesis by EphB/ephrin-B2 signaling between endothelial cells and surrounding mesenchymal cells
复制标题
DOI：
10.1182/blood.v100.4.1326.h81602001326_1326_1333
复制
发表时间：
2002-08-15
期刊：
影响因子：
20.3
通讯作者：
Suda, T
中科院分区：
文献类型：
--
作者：
Oike, Y;Ito, Y;Suda, T
虽然控制血管生成的细胞和分子机制才刚刚开始被理解，通过内皮限制性受体，特别是受体酪氨酸激酶的信号转导，已被证明在这些事件中发挥关键作用。最近的报道表明，EphB受体酪氨酸激酶和它们的跨膜型ephrin-B2配体在胚胎血管系统中发挥重要作用。这些研究表明，由于双向EphB/ephrin-B2信号传导引起的细胞对细胞的排斥作用可能对血管发育至关重要，类似于神经元发育所描述的机制。为了验证这一假设，我们通过产生在普遍存在的组成型启动子CMV增强子-β-肌动蛋白启动子-β-珠蛋白剪接受体（CAG）的控制下表达肝配蛋白-B2的转基因（CAGp-ephrin-B2 Tg）小鼠，破坏了EphB/肝配蛋白-B2的体内精确表达模式。这些小鼠显示出异常的体节间血管节段性排列，而在Tie-2 p-ephrin-82 Tg小鼠中未观察到这种异常，其中ephrin-B2仅在血管内皮细胞（EC）中过表达。这一发现表明，不表达肝配蛋白-B2的EC改变表达EphB受体的EC迁移到通常不表达肝配蛋白-B2的体间区。CAGpephrin-B2 Tg小鼠在新生期由于血管平滑肌细胞向升主动脉的募集缺陷而死于主动脉夹层动脉瘤。内皮细胞和周围间充质细胞之间的EphB/ephrin-B2信号传导在血管发生、血管生成和血管成熟中起重要作用。(C)2002年，美国血液学会。
Although the cellular and molecular mechanisms governing angiogenesis are only beginning to be understood, signaling through endothelial-restricted receptors, particularly receptor tyrosine kinases, has been shown to play a pivotal role in these events. Recent reports show that EphB receptor tyrosine kinases and their transmembrane-type ephrin-B2 ligands play essential roles in the embryonic vasculature. These studies suggest that cell-to-cell repellent effects due to bidirectional EphB/ephrin-B2 signaling may be crucial for vascular development, similar to the mechanism described for neuronal development. To test this hypothesis, we disrupted the precise expression pattern of EphB/ephrin-B2 In vivo by generating transgenic (CAGp-ephrin-B2 Tg) mice that express ephrin-B2 under the control of a ubiquitous and constitutive promoter, CMV enhancer-beta-actin promoter-beta-globin splicing acceptor (CAG). These mice displayed an abnormal segmental arrangement of Intersomitic vessels, while such anomalies were not observed in Tie-2p-ephrin-82 Tg mice in which ephrin-B2 was overexpressed In only vascular endothelial cells (ECs). This finding suggests that non-ECs expressing ephrin-B2 alter the migration of ECs expressing EphB receptors Into the intersomitic region where ephrin-B2 expression is normally absent. CAGpephrin-B2 Tg mice show sudden death at neonatal stages from aortic dissecting aneurysms due to defective recruitment of vascular smooth muscle cells to the ascending aorta. EphB/ephrin-B2 signaling between endothelial cells and surrounding mesenchymal cells plays an essential role in vasculogenesis, angiogenesis, and vessel maturation. (C) 2002 by The American Society of Hematology.