Cell signaling in regulation of the barrier integrity of the corneal endothelium.
Cell signaling in regulation of the barrier integrity of the corneal endothelium.
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DOI：
10.1016/j.exer.2011.09.009
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发表时间：
2012-02
影响因子：
3.4
通讯作者：
Srinivas SP
中科院分区：
文献类型：
--
作者：
Srinivas SP
角膜内皮的屏障完整性，这是由其紧密连接和粘附连接所赋予的，对于维持角膜基质的消肿是至关重要的。尽管特征性地渗漏，但是屏障完整性限制了液体渗漏到基质中，使得渗漏速率不超过朝向房水的内皮主动液体运输速率。在分子水平上，屏障的完整性受到肌动蛋白细胞骨架和微管的影响，它们通过各种连接蛋白与紧密连接和粘附连接偶联。由于细胞骨架受到Rho家族小GTP酶和p38 MAP激酶等的影响，许多病理生理刺激诱导细胞骨架的可塑性，从而引起屏障完整性的动态调节。本文综述了几种生物活性因子通过改变肌动蛋白细胞骨架和/或微管分解对角膜内皮屏障完整性的影响。主要关注TNF-α（肿瘤坏死因子-α）的作用，TNF-α是在同种异体移植排斥反应和前葡萄膜炎期间眼内环境中发现的促炎分子。这种细胞因子激发p38 MAP激酶的急性激活，诱导微管的解体，破坏连接周围的肌动球蛋白环，并伴随着破坏屏障的完整性。TNF-α的这些作用可通过稳定微管、与选择性p38 MAP激酶抑制剂共处理、通过A2 B受体升高细胞内cAMP或直接暴露于毛喉素来抑制。总的来说，角膜水肿后的一个潜在的破坏内皮屏障的完整性，可以挽救通过抑制特定的细胞信号传导机制。
The barrier integrity of the corneal endothelium, which is conferred by its tight and adherens junctions, is critical for the maintenance of deturgescence of the corneal stroma. Although characteristically leaky, the barrier integrity restricts fluid leakage into the stroma such that the rate of leak does not exceed the rate of the endothelial active fluid transport directed toward the aqueous humor. At a molecular level, the barrier integrity is influenced by the actin cytoskeleton and microtubules, which are coupled to tight and adherens junctions via a variety of linker proteins. Since the cytoskeleton is affected by Rho family small GTPases and p38 MAP kinase, among others, many pathophysiological stimuli induce plasticity to the cytoskeleton and thereby elicit dynamic regulation of the barrier integrity. This review presents an overview of the impact of several bioactive factors on the barrier integrity of the corneal endothelium through altered actin cytoskeleton and/or disassembly of microtubules. The main focus is on the effect of TNF-α (tumor necrosis factor-α) which is a pro-inflammatory molecule found in the intraocular milieu during allograft rejection and anterior uveitis. This cytokine elicits acute activation of p38 MAP kinase, induces disassembly of microtubules, disrupts the peri-junctional actomyosin ring, and concomitantly breaks down the barrier integrity. These effects of TNF-α could be inhibited by stabilizing the microtubules, co-treating with a selective p38 MAP kinase inhibitor, and elevating intracellular cAMP via A2B receptors or direct exposure to forskolin. Overall, the corneal edema following a potential breakdown of the endothelial barrier integrity can be rescued pharmacologically by inhibiting specific cell-signaling mechanisms.
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影响因子：
3.4
作者：
Capaldo, Christopher T.;Nusrat, Asma
通讯作者：
Nusrat, Asma
影响因子：
--
作者：
GOLDBLUM, SE;DING, XD;CAMPBELLWASHINGTON, J
通讯作者：
CAMPBELLWASHINGTON, J
影响因子：
4.8
作者：
Birukova, AA;Birukov, KG;Verin, AD
通讯作者：
Verin, AD
影响因子：
3.3
作者：
Johnsen-Soriano, Siv;Sancho-Tello, Maria;Javier Romero, Francisco
通讯作者：
Javier Romero, Francisco
影响因子：
5.6
作者：
Birukova, AA;Birilikov, KG;Verin, AD
通讯作者：
Verin, AD