Ramos Carla J, Antonetti David A
a Department of Ophthalmology and Visual Sciences , University of Michigan , Ann Arbor , MI USA.
Tissue Barriers. 2017 Jul 3;5(3):e1339768. doi: 10.1080/21688370.2017.1339768. Epub 2017 Jun 9.
Maintenance and regulation of the vascular endothelial cell junctional complex is critical for proper barrier function of the blood-brain barrier (BBB) and the highly related blood-retinal barrier (BRB) that help maintain proper neuronal environment. Recent research has demonstrated that the junctional complex is actively maintained and can be dynamically regulated. Studies focusing on the mechanisms of barrier formation, maintenance, and barrier disruption have been of interest to understanding development of the BBB and BRB and identifying a means for therapeutic intervention for diseases ranging from brain tumors and dementia to blinding eye diseases. Research has increasingly revealed that small GTPases play a critical role in both barrier formation and disruption mechanisms. This review will summarize the current data on small GTPases in barrier regulation with an emphasis on the EPAC-Rap1 signaling pathway to Rho in endothelial barriers, as well as explore its potential involvement in paracellular flux and transcytosis regulation.
维持和调节血管内皮细胞连接复合体对于血脑屏障（BBB）和高度相关的血视网膜屏障（BRB）的正常屏障功能至关重要，这两种屏障有助于维持适当的神经元环境。最近的研究表明，连接复合体能够被积极维持并可动态调节。专注于屏障形成、维持和破坏机制的研究，对于理解血脑屏障和血视网膜屏障的发育以及确定针对从脑肿瘤、痴呆到致盲眼病等疾病的治疗干预手段具有重要意义。研究越来越多地揭示，小GTP酶在屏障形成和破坏机制中都起着关键作用。本综述将总结关于小GTP酶在屏障调节方面的现有数据，重点关注内皮屏障中从EPAC-Rap1信号通路到Rho的过程，同时探讨其在细胞旁通量和转胞吞作用调节中的潜在参与情况。
