期刊
TOXICOLOGY AND APPLIED PHARMACOLOGY
卷 279, 期 2, 页码 163-172出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.taap.2014.05.013
关键词
Claudin 2; Tight junction; Water permeability; Proximal tubule; Cyclosporine A; Trans-epithelial electrical resistance
资金
- European Union's 7th Framework Programme (FP7) [202222]
- FP7 project DETECTIVE [266838]
- Innovative Medicines Initiative Joint Undertaking (IMI JU) project StemBANCC [115439]
- FP7
- EFPIA
- Predict-IV
Claudins are the major proteins of the tight junctions and the composition of claudin subtypes is decisive for the selective permeability of the paracellular route and thus tissue specific function. Their regulation is complex and subject to interference by several factors, including oxidative stress. Here we show that exposure of cultured human proximal tubule cells (RPTEC/TERT1) to the immunosuppressive drug cyclosporine A (CsA) induces an increase in transepithelial electrical resistance (TEER), a decrease in dome formation (on solid growth supports) and a decrease in water transport (on microporous growth supports). In addition, CsA induced a dramatic decrease in the mRNA for the pore forming claudins -2 and -10, and the main subunits of the Na+/K+ ATPase. Knock down of claudin 2 by shRNA had no discernable effect on TEER or dome formation but severely attenuated apical to basolateral water reabsorption when cultured on microporous filters. Generation of an osmotic gradient in the basolateral compartment rescued water transport in claudin 2 knock down cells. Inhibition of Na+/K+ ATPase with ouabain prevented dome formation in both cell types. Taken together these results provide strong evidence that dome formation is primarily due to transcellular water transport following a solute osmotic gradient However, in RPTEC/TERT1 cells cultured on filters under iso-osmotic conditions, water transport is primarily paracellular, most likely due to local increases in osmolarity in the intercellular space. In conclusion, this study provides strong evidence that claudin 2 is involved in paracellular water transport and that claudin 2 expression is sensitive to compound induced cellular stress. (C) 2014 Elsevier Inc. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据