Shay-Salit Ayelet, Shushy Moran, Wolfovitz Efrat, Yahav Hava, Breviario Ferruccio, Dejana Elisabetta, Resnick Nitzan
Department of Anatomy and Cell Biology, Bruce Rappaport Research Institute and the Rappaport Faculty of Medicine, Technion, Haifa 31096, Israel.
Proc Natl Acad Sci U S A. 2002 Jul 9;99(14):9462-7. doi: 10.1073/pnas.142224299. Epub 2002 Jun 21.
Blood-flow interactions with the vascular endothelium represents a specialized example of mechanical regulation of cell function that has important physiological and pathophysiological cardiovascular consequences. Yet, the mechanisms of mechanostransduction are not understood fully. This study shows that shear stress induces a rapid induction as well as nuclear translocation of the vascular endothelial growth factor (VEGF) receptor 2 and promotes the binding of the VEGF receptor 2 and the adherens junction molecules, VE-cadherin and beta-catenin, to the endothelial cytoskeleton. These changes are accompanied by the formation of a complex containing the VEGF receptor 2-VE-cadherin-beta-catenin. In endothelial cells lacking VE-cadherin, shear stress did not augment nuclear translocation of the VEGF receptor 2 and phosphorylation of Akt1 and P38 as well as transcriptional induction of a reporter gene regulated by a shear stress-responsive promoter. These results suggest that VEGF receptor 2 and the adherens junction act as shear-stress cotransducers, mediating the transduction of shear-stress signals into vascular endothelial cells.
血流与血管内皮之间的相互作用代表了细胞功能机械调节的一个特殊例子，这对心血管生理和病理生理具有重要影响。然而，机械转导的机制尚未完全明了。本研究表明，剪切应力可诱导血管内皮生长因子（VEGF）受体2的快速诱导及核转位，并促进VEGF受体2与黏附连接分子血管内皮钙黏蛋白（VE-cadherin）和β-连环蛋白与内皮细胞骨架的结合。这些变化伴随着包含VEGF受体2-VE-cadherin-β-连环蛋白复合物的形成。在缺乏VE-cadherin的内皮细胞中，剪切应力不会增强VEGF受体2的核转位、Akt1和P38的磷酸化以及由剪切应力反应性启动子调控的报告基因的转录诱导。这些结果表明，VEGF受体2和黏附连接作为剪切应力共转导器，介导剪切应力信号转导至血管内皮细胞。
