Cellular and molecular regulation of vascular permeability.
Cellular and molecular regulation of vascular permeability.
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DOI：
10.1160/th12-09-0678
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发表时间：
2013-03
影响因子：
6.7
通讯作者：
Iruela-Arispe ML
中科院分区：
文献类型：
--
作者：
Goddard LM;Iruela-Arispe ML
血管通透性是一个高度协调的过程，它整合了囊泡运输、复杂的连接重排以及精细的细胞骨架动力学。针对细胞外环境，先前假定这三种细胞活动并行发挥作用，以调节血液和组织之间溶质的通过。然而，血管通透性领域的新进展强调了跨细胞途径和旁细胞途径之间的相互依存关系、黏附连接和紧密连接之间的交叉通讯，以及周细胞对内皮细胞屏障相关基因表达的指导作用。此外，在理解急性通透性事件后有助于屏障恢复的分子基础以及阐明通透性介质引发的依赖于环境的信号传导的重要性方面已经付出了巨大努力。最后，最近的研究结果揭示了转录因子在血管通透性协调中的一种未预料到的作用，并阐明了连接复合物如何将信号传递到细胞核以控制屏障功能。本综述的目的是提供关于血管通透性的简洁且最新的观点，讨论分子和细胞调控方面的最新进展，并介绍有关跨内皮运输所涉及的核心机制的综合信息。
Vascular permeability is a highly coordinated process that integrates vesicular trafficking, complex junctional rearrangements, and refined cytoskeletal dynamics. In response to the extracellular environment, these three cellular activities have been previously assumed to work in parallel to regulate the passage of solutes between the blood and tissues. New developments in the area of vascular permeability, however have highlighted the interdependence between trans- and para-cellular pathways, the cross-communication between adherens and tight junctions, and the instructional role of pericytes on endothelial expression of barrier-related genes. Additionally, significant effort has been placed in understanding the molecular underpinings that contribute to barrier restoration following acute permeability events and in clarifying the importance of context-dependent signaling initiated by permeability mediators. Finally, recent findings have uncovered an unpredicted role for transcription factors in the coordination of vascular permeability and clarified how junctional complexes can transmit signals to the nucleus to control barrier function. The goal of this review is to provide a concise and updated view of vascular permeability, discuss the most recent advances in molecular and cellular regulation, and introduce integrated information on the central mechanisms involved in trans-endothelial transport.