Lee Sae-Won, Kim Woo Jean, Jun Hyoung-Oh, Choi Yoon Kyung, Kim Kyu-Won
Clinical Research Institute, Seoul National University Hospital, Seoul 110-744, Korea.
Int J Mol Med. 2009 Feb;23(2):279-84.
Brain microvessels possess barrier structures comprising tight junctions which are critical for the maintenance of central nervous system homeostasis. Brain vascular diseases, such as ischemic stroke damage to blood-brain barrier, increase the vascular permeability, and then lead to vasogenic brain edema. Herein, we examined whether angiopoietin-1 (Ang-1) could regulate zonula occludens-2 (ZO-2) expression and counteract vascular endothelial growth factor (VEGF)-induced vascular permeability. When we treated brain microvascular endothelial cells with Ang-1, Ang-1 caused a time- and dose-dependent increase of ZO-2 and down-regulation in endothelial permeability. VEGF, one of the key regulators of ischemia-induced vascular permeability, increased endothelial cell permeability in vitro, whereas, Ang-1 reversed this VEGF effect by up-regulating ZO-2 expression. Additionally, the recovery effect of Ang-1 on permeability was strongly blocked by siRNA against ZO-2. Collectively, our results suggest that Ang-1 shows anti-permeability activity through up-regulation of ZO-2.
脑微血管具有由紧密连接组成的屏障结构，这些紧密连接对于维持中枢神经系统的稳态至关重要。脑血管疾病，如缺血性中风对血脑屏障的损害，会增加血管通透性，进而导致血管性脑水肿。在此，我们研究了血管生成素-1（Ang-1）是否能调节闭合蛋白-2（ZO-2）的表达，并对抗血管内皮生长因子（VEGF）诱导的血管通透性。当我们用Ang-1处理脑微血管内皮细胞时，Ang-1导致ZO-2呈时间和剂量依赖性增加，并降低内皮通透性。VEGF是缺血诱导的血管通透性的关键调节因子之一，在体外可增加内皮细胞通透性，而Ang-1通过上调ZO-2表达逆转了这种VEGF效应。此外，针对ZO-2的小干扰RNA（siRNA）强烈阻断了Ang-1对通透性的恢复作用。总体而言，我们的结果表明，Ang-1通过上调ZO-2表现出抗通透性活性。
