Rho GTP酶家族分子及其调节因子与血管内皮屏障功能间的关系  

Relationship between Rho GTPase family regulation and vascular endothelial barrier function

作　　者：赵宗璇 潘燕[1] ZHAO Zong-xuan;PAN Yan(School of Basic Medical Sciences, Peking University, Beijing 100191, China)

机构地区：[1]北京大学基础医学院,北京100191

出　　处：《药学学报》2019年第4期587-593,共7页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金资助项目(81773765;81270049;81874318;81673453;81473235)

摘　　要：血管内皮屏障功能的受损涉及到多种病理生理状态的发生与进展,血管内皮屏障的完整性受到细胞骨架及细胞间连接的调控,而Rho-GTP酶在其中起着核心作用。目前已经发现RhoA、Rac1、Cdc42、RhoB参与调节血管内皮屏障功能。这些Rho-GTP酶在血管内皮屏障功能的调节中有着双重作用,与其亚细胞定位密切相关。当炎症因子作用于血管内皮细胞, RhoA广泛分布于细胞各处引起微丝聚集,产生急性细胞收缩破坏血管内皮屏障。在新生血管内皮细胞中, RhoA则大量聚集于细胞膜附近,参与细胞间连接的产生与成熟。Rac1及Cdc42在静息状态下能够降低丝切蛋白的活性,减少细胞膜附近细胞骨架重构,参与维持血管内皮屏障的稳定。而Cdc42在血管内皮完整性受损时能够迅速聚集于细胞皮质处,活化肌球蛋白Ⅱ,促进黏合连接的生成,参与早期血管内皮屏障完整性的恢复。本文就Rho GTP酶对血管内皮屏障完整性的调节进行概述。Injury of vascular endothelial barrier function is implicated in several pathophysiological processes. The integrity of vascular endothelium is regulated by cytoskeleton and cell-cell junctions. Small guanosine triphosphatases of the Rho family (Rho GTPases) are known to play a central role in vascular endothelial barrier function. It has been reported that RhoA, Rac1, Cdc42 and RhoB are involved and they exert both positive and negative effect on endothelial barrier integrity, depending on their subcellular location. When inflammatory factors such as thrombin attack the vascular endothelial cells, GEF of RhoA will be widely distributed throughout the cells. Thus, activated RhoA causes aggregation of F-actin fibers in a short time and disrupts the vascular endothelial barrier, a process named acute cell contraction. However, RhoA may also induce the production and maturation of intercellular junctions in new cells. Rac1 and Cdc42 help to maintain the integrity of vascular endothelial barrier at the resting state. They cause the phosphorylation of LIM kinase and inhabitation of cofilin, resulting in less remodeling of cytoskeletal in the vascular endothelial cells. On the other hand, Cdc42 can translocate to the cortex rapidly after a stimulation, where Cdc42 will activate the myosin Ⅱ and promote the reorganization of adjective junction to facilitate the recovery of vascular endothelial barrier. In this review, we overviewed how Rho GTPases regulate the vascular endothelial barrier integrity.

关 键 词：内皮 血管 ρGTP结合蛋白质类 毛细血管通透性 

分 类 号：R963[医药卫生—微生物与生化药学]