Regulation of endothelial permeability by Src kinase signaling: Vascular leakage versus transcellular transport of drugs and macromolecules
Regulation of endothelial permeability by Src kinase signaling: Vascular leakage versus transcellular transport of drugs and macromolecules
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DOI：
10.1016/j.cbi.2007.08.006
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发表时间：
2008-01-30
影响因子：
5.1
通讯作者：
Minshall, Richard D.
中科院分区：
文献类型：
--
作者：
Hu, Guochang;Place, Aaron T.;Minshall, Richard D.
内皮的一个重要功能是调节液体和溶质穿过半透性血管内皮屏障的转运。已经确定了两种控制内皮屏障功能的细胞途径。正常限制性的细胞旁途径，当在粘附物和紧密连接复合物水平的内皮细胞之间诱导间隙时，其在炎症期间可能变得“渗漏”，以及跨细胞途径，其通过源自细胞表面小窝的囊泡载体中的转胞吞作用转运白蛋白大小的血浆蛋白。在非炎症性疾病期间，小窝介导的转运可能是液相分子以及与白蛋白紧密结合的脂质、激素和肽的血管通透性调节的主要机制。Src家族蛋白酪氨酸激酶参与上游信号通路，通过细胞旁和跨细胞途径导致内皮细胞通透性过高。内皮屏障功能障碍不仅影响血管稳态和细胞代谢，而且还控制药物递送到下层细胞和组织。在这篇综述中，我们讨论了Src信号在调节细胞旁和跨细胞内皮渗透性途径中的作用以及对内源性大分子和药物递送的影响。(c)2007爱思唯尔爱尔兰有限公司保留所有权利。
An important function of the endothelium is to regulate the transport of liquid and solutes across the semi-permeable vascular endothelial barrier. Two cellular pathways have been identified controlling endothelial barrier function. The normally restrictive paracellular path way, which can become "leaky" during inflammation when gaps are induced between endothelial cells at the level of adherens and tight junctional complexes, and the transcellular pathway, which transports plasma proteins the size of albumin via transcytosis in vesicle carriers originating from cell surface caveolae. During non-inflammatory conditions, caveolae-mediated transport may be the primary mechanism of vascular permeability regulation of fluid phase molecules as well as lipids, hormones, and peptides that bind avidly to albumin. Src family protein tyrosine kinases have been implicated in the upstream signaling pathways that lead to endothelial hyperpermeability through both the paracellular and transcellular pathways. Endothelial barrier dysfunction not only affects vascular homeostasis and cell metabolism, but also governs drug delivery to underlying cells and tissues. In this review of the field, we discuss the current understanding of Src signaling in regulating paracellular and transcellular endothelial permeability pathways and effects on endogenous macromolecule and drug delivery. (c) 2007 Elsevier Ireland Ltd. All rights reserved.