Protective effect of dexamethasone against hypoxia-induced disruption of barrier function in human corneal epithelial cells
Protective effect of dexamethasone against hypoxia-induced disruption of barrier function in human corneal epithelial cells
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DOI：
10.1016/j.exer.2011.02.013
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发表时间：
2011-05-01
影响因子：
3.4
通讯作者：
Nishida, Teruo
中科院分区：
文献类型：
--
作者：
Kimura, Kazuhiro;Teranishi, Shinichiro;Nishida, Teruo
角膜上皮起着屏障的作用，保护角膜免受感染生物和毒素等外界因素的侵袭，从而促进角膜的动态平衡。上皮细胞的屏障功能依赖于相邻上皮细胞之间紧密和粘连连接的形成。我们之前已经证明，低氧通过影响紧密连接来破坏培养的人角膜上皮(HCE)细胞的屏障功能。我们现在研究了地塞米松对低氧诱导的HCE细胞屏障破坏的影响。跨皮细胞电阻测定显示，地塞米松以浓度依赖的方式抑制低氧引起的HCE细胞屏障功能的降低。地塞米松可抑制低氧诱导的邻近HCE细胞边界紧密连接蛋白ZO-1的缺失(免疫荧光分析显示)和低氧诱导的ZO-1表达下调(免疫印迹分析显示)，但对紧密连接蛋白occludin或黏附连接蛋白E-cadherin和β-catenin的表达和分布没有影响。此外，地塞米松可减弱缺氧诱导的HCE细胞肌动蛋白细胞骨架的重组、局部粘连的形成以及肌球蛋白轻链激酶表达的上调。因此，我们的结果提示地塞米松通过维持ZO-1的分布和表达以及肌动蛋白细胞骨架的组织来保护角膜上皮细胞免受缺氧诱导的屏障功能的破坏。皇冠版权所有(C)2011由爱思唯尔有限公司出版。保留所有权利。
The corneal epithelium functions as a barrier to protect the cornea from external agents such as infectious organisms and toxins and thereby contributes to corneal homeostasis. The barrier function of epithelia is dependent on the formation of tight and adherens junctions between adjacent epithelial cells. We have previously shown that hypoxia disrupts the barrier function of cultured human corneal epithelial (HCE) cells by affecting tight junctions. We have now examined the effect of dexamethasone on this barrier disruption induced by hypoxia in HCE cells. Measurement of transepithelial electrical resistance revealed that the hypoxia-induced decrease in the barrier function of HCE cells was inhibited by dexamethasone in a concentration-dependent manner. The hypoxia-induced loss of the tight junction protein ZO-1 from the borders of adjacent HCE cells (as revealed by immunofluorescence analysis) as well as the hypoxia-induced down-regulation of ZO-1 expression (as revealed by immunoblot analysis) were also inhibited by dexamethasone, whereas this drug had no effect on the expression or distribution of the tight junction protein occludin or of the adherens junction proteins E-cadherin and beta-catenin. Moreover, dexamethasone attenuated the reorganization of the actin cytoskeleton, the formation of focal adhesions, and the up-regulation of myosin light chain kinase expression induced by hypoxia in HCE cells. Our results thus suggest that dexamethasone protects corneal epithelial cells from the hypoxia-induced disruption of barrier function by maintaining the distribution and expression of ZO-1 as well as the organization of the actin cytoskeleton. Crown Copyright (c) 2011 Published by Elsevier Ltd. All rights reserved.