摘要
密封蛋白-5,一种显性紧密连接(TJs)蛋白,在维持血脑屏障功能和视网膜屏障中发挥重要作用。本研究旨在调查初期培养的人类视网膜色素上皮细胞(HRPECs)和人类视网膜内皮细胞(HRECs)中密封蛋白-5 超表达在与密封蛋白-1和-2的交互作用和屏障功能中的作用。慢病毒被用来调节视网膜细胞中密封蛋白-5的超表达。在转染组中检测到密封蛋白-5显著增加的mRNA和蛋白水平。 转染细胞在转染孔膜中生长三周后,一个稳定的单层细胞屏障模型在体外被建立。密封蛋白表达分析表明密封蛋白-5的超表达显著增加了密封蛋白-1的表达,而在mRNA和蛋白水平上均减低了密封蛋白-2的表达。Co-IP实验和屏障功能测试表明密封蛋白-5超表达促进其与密封蛋白-1和密封蛋白-2 的相互作用,并且加强视网膜细胞的屏障功能。有趣的是,密封蛋白-5的外源性表达诱发了视网膜细胞中密封蛋白-5和密封蛋白-1 或-2之间的一种新型相互作用类型,这没有内生性密封蛋白-5表达。另外,密封蛋白-5 超表达降低细胞迁移和体外导管形成的出芽能力。本研究表明密封蛋白-5 在视网膜屏障形成中起积极调节作用。密封蛋白的组成部分和它们之间的相互作用可被调节,这种动态属性对于TJs的功能很重要,从视网膜屏障的完整性到交联信号机制。
关键词: 屏障功能,密封蛋白-5,密封蛋白-1,密封蛋白-2,相互作用,紧密连接。
Current Molecular Medicine
Title:The Effect of Claudin-5 Overexpression on the Interactions of Claudin-1 and -2 and Barrier Function in Retinal Cells
Volume: 14 Issue: 9
Author(s): R. Tian, Y. Luo, Q. Liu, M. Cai, J. Li, W. Sun, J. Wang, C. He, Y. Liu and X. Liu
Affiliation:
关键词: 屏障功能,密封蛋白-5,密封蛋白-1,密封蛋白-2,相互作用,紧密连接。
摘要: Claudin-5, one of the dominant tight junctions (TJs) proteins, plays an important role in maintaining the barrier function in the blood brain and retinal barrier. This study aimed to investigate the effect of claudin-5 overexpression on the interactions of claudin-1 and -2 and barrier functions in primary cultured human retinal pigment epithelium cells (HRPECs) and human retina endothelial cells (HRECs). Lentivirus was used to mediate the overexpression of claudin-5 in retinal cells. Significantly increased mRNA and protein levels of claudin-5 were detected in the transfection group. After the transfected cells grew on the transwell membrane for three weeks, a stable monolayer cell barrier model was established in vitro. The claudins expressions analysis showed that overexpressed claudin-5 significantly increased the expression of claudin-1, while it decreased the expression of claudin-2 in both mRNA and protein level. Co-IP experiments and barrier function assay revealed that claudin-5 overexpression promoted the interactions of claudin-1 and claudin-2 and enhanced the barrier function of retinal cells. Intriguingly, the exogenous expression of claudin-5 induced new interaction pattern between claudin-5 and claudin-1 or -2 in HRPECs, which do not have endogenous claudin-5 expression. In addition, claudin-5 overexpression decreased cell mobility and the sprouting capability of vessel tube formation in vitro. This study demonstrated that claudin-5 has a positive regulation in the formation of retinal barrier. Claudin elements and their interactions can be modulated and that such dynamic properties are important for the functions of TJs, ranging from the regulation of retinal barrier integrity to junction-associated signaling mechanisms.
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Cite this article as:
R. Tian, Y. Luo, Q. Liu, M. Cai, J. Li, W. Sun, J. Wang, C. He, Y. Liu and Liu X., The Effect of Claudin-5 Overexpression on the Interactions of Claudin-1 and -2 and Barrier Function in Retinal Cells, Current Molecular Medicine 2014; 14 (9) . https://dx.doi.org/10.2174/1566524014666141015160355
DOI https://dx.doi.org/10.2174/1566524014666141015160355 |
Print ISSN 1566-5240 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5666 |
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