Activation of integrins in endothelial cells by fluid shear stress mediates Rho-dependent cytoskeletal alignment
Activation of integrins in endothelial cells by fluid shear stress mediates Rho-dependent cytoskeletal alignment
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DOI：
10.1093/emboj/20.17.4639
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发表时间：
2001-09-03
期刊：
影响因子：
11.4
通讯作者：
Schwartz, MA
中科院分区：
文献类型：
--
作者：
Tzima, E;del Pozo, MA;Schwartz, MA
流体切应力是血管重塑和动脉粥样硬化形成的关键决定因素。整联蛋白和小的GT3 Rho都参与内皮细胞对剪切的反应，但其机制知之甚少。我们现在表明，剪切应力迅速刺激整合素α v β 3在牛主动脉内皮细胞中的构象激活，随后增加其与细胞外基质（ECM）蛋白的结合。剪切诱导的新整合素与ECM的结合诱导Rho的瞬时失活，类似于将悬浮细胞接种在ECM蛋白上时所见。这种短暂的抑制对于细胞骨架在流动方向上的排列是必要的。因此，这些结果定义了整合素和Rho在导致内皮细胞适应流动的途径中的作用。
Fluid shear stress is a critical determinant of vascular remodeling and atherogenesis. Both integrins and the small GTPase Rho are implicated in endothelial cell responses to shear but the mechanisms are poorly understood. We now show that shear stress rapidly stimulates conformational activation of integrin alphav beta3 in bovine aortic endothelial cells, followed by an increase in its binding to extracellular cell matrix (ECM) proteins. The shear-induced new integrin binding to ECM induces a transient inactivation of Rho similar to that seen when suspended cells are plated on ECM proteins. This transient inhibition is necessary for cytoskeletal alignment in the direction of flow. The results therefore define the role of integrins and Rho in a pathway leading to endothelial cell adaptation to flow.