RhoA GTPase regulates radiation-induced alterations in endothelial cell adhesion and migration.
RhoA GTPase regulates radiation-induced alterations in endothelial cell adhesion and migration.
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DOI：
10.1016/j.bbrc.2011.09.150
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发表时间：
2011-11
影响因子：
3.1
通讯作者：
M. Rousseau;M. Gaugler;A. Rodallec;S. Bonnaud;F. Paris;I. Corre
中科院分区：
文献类型：
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作者：
M. Rousseau;M. Gaugler;A. Rodallec;S. Bonnaud;F. Paris;I. Corre
微血管内皮细胞是电离辐射的主要靶点，是辐射所致血管早期功能障碍的主要原因。参与内皮细胞对电离辐射反应的分子信号通路，尽管被越来越多地研究，但仍然需要精确的表征。小分子GTP酶RhoA及其效应器ROCK是参与内皮细胞许多功能的重要信号分子。最近的研究证实，RhoA/ROCK与辐射引起的内皮通透性增加有关，但辐射引起的其他内皮功能改变可能也需要RhoA蛋白。人微血管内皮细胞经Y-27632(ROCK抑制剂)处理或经RhoA干扰使其失效的人微血管内皮细胞HMEC-1受到15Gy射线照射。我们显示了辐射诱导的RhoA的快速激活，导致肌动蛋白细胞骨架的深度重组，并迅速形成应力纤维。Y-27632预处理或RhoA耗竭不影响电离辐射诱导的内皮细胞早期凋亡。内皮细胞对纤维连接蛋白的黏附和局部黏附的形成在辐射反应中以RhoA/ROCK依赖的方式增加。与其促进黏附的作用一致，电离辐射也减少了内皮细胞的迁移，这种抑制需要RhoA。这些结果突出了RhoA GTPase在电离辐射诱导的与肌动蛋白细胞骨架相关的基本内皮功能的解除调节中的作用。
Endothelial cells of the microvasculature are major target of ionizing radiation, responsible of the radiation-induced vascular early dysfunctions. Molecular signaling pathways involved in endothelial responses to ionizing radiation, despite being increasingly investigated, still need precise characterization. Small GTPase RhoA and its effector ROCK are crucial signaling molecules involved in many endothelial cellular functions. Recent studies identified implication of RhoA/ROCK in radiation-induced increase in endothelial permeability but other endothelial functions altered by radiation might also require RhoA proteins. Human microvascular endothelial cells HMEC-1, either treated with Y-27632 (inhibitor of ROCK) or invalidated for RhoA by RNA interference were exposed to 15Gy. We showed a rapid radiation-induced activation of RhoA, leading to a deep reorganisation of actin cytoskeleton with rapid formation of stress fibers. Endothelial early apoptosis induced by ionizing radiation was not affected by Y-27632 pre-treatment or RhoA depletion. Endothelial adhesion to fibronectin and formation of focal adhesions increased in response to radiation in a RhoA/ROCK-dependent manner. Consistent with its pro-adhesive role, ionizing radiation also decreased endothelial cells migration and RhoA was required for this inhibition. These results highlight the role of RhoA GTPase in ionizing radiation-induced deregulation of essential endothelial functions linked to actin cytoskeleton.