Roles of microtubule dynamics and small GTPase rac in endothelial cell migration and lamellipodium formation under flow
Roles of microtubule dynamics and small GTPase rac in endothelial cell migration and lamellipodium formation under flow
复制标题
DOI：
10.1159/000067202
复制
发表时间：
2002-11-01
影响因子：
1.7
通讯作者：
Chien, S
中科院分区：
文献类型：
--
作者：
Hu, YL;Li, S;Chien, S
内皮细胞（EC）的迁移是血管发育和伤口愈合所必需的。本文研究了微管（MT）动力学和小GTPase Rac在流体剪切应力诱导的牛主动脉内皮细胞（BAECs）板足突出和迁移增强中的作用。剪切应力增加板足突和细胞迁移。用mt稳定剂紫杉醇（紫杉醇）治疗baec，在静态组和剪切组均能抑制板足突，降低迁移速度。紫杉醇冲洗后，板足突和细胞迁移在流动方向上均增加。紫杉醇处理也降低了剪切诱导的Rac活化。转染ra1显性阴性突变体的BAECs在静态和剪切条件下抑制板足突和细胞迁移。转染活化的Rac1突变体诱导板足向各个方向迁移，并减弱剪切诱导的迁移，这表明在静态和剪切条件下，适当水平的Rac活性和极化板足突出对细胞迁移很重要。我们的研究结果表明，板状足的极化突出驱动EC在流动下的定向迁移需要MT动力学和最佳Rac激活。版权所有(C) 2002 S. Karger AG，巴塞尔。
Endothelial cell (EC) migration is required for vascular development and wound healing. We investigated the roles of microtubule (MT) dynamics and the small GTPase Rac in the fluid shear stress-induced protrusion of lamellipodia and enhancement of migration of bovine aortic ECs (BAECs). Shear stress increased lamellipodial protrusion and cell migration. Treating BAECs with paclitaxel (Taxol), an MT-stabilizing agent, inhibited lamellipodial protrusion and reduced migration speed in both the static and sheared groups. After Taxol washout, both lamellipodial protrusion and cell migration increased in the flow direction. Taxol treatment also decreased the shear-induced Rac activation. Transfection of BAECs with a dominant negative mutant of Rac1 inhibited lamellipodial protrusion and cell migration under static and shear conditions. Transfection with an activated mutant of Rac1 induced lamellipodia in all directions and attenuated the shear-induced migration, suggesting that an appropriate level of Rac activity and a polarized lamellipodial protrusion are important for cell migration under static and shear conditions. Our findings suggest that MT dynamics and optimum Rac activation are required for the polarized protrusion of lamellipodia that drives the directional EC migration under flow. Copyright (C) 2002 S. Karger AG, Basel.