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Open AccessArticle

Claudin-7 Modulates Cl and Na+ Homeostasis and WNK4 Expression in Renal Collecting Duct Cells

1
Department of Anatomy and Cell Biology, Brody School of Medicine, East Carolina University, Greenville, NC 27834, USA
2
Institute of Hypoxia Medicine, School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou 325035, China
3
East Carolina Diabetes and Obesity Institute, East Carolina University, Greenville, NC 27834, USA
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(15), 3798; https://doi.org/10.3390/ijms20153798
Received: 11 July 2019 / Accepted: 30 July 2019 / Published: 3 August 2019
(This article belongs to the Special Issue The Tight Junction and Its Proteins: More Than Just a Barrier)
Claudin-7 knockout (CLDN7−/−) mice display renal salt wasting and dehydration phenotypes. To address the role of CLDN7 in kidneys, we established collecting duct (CD) cell lines from CLDN7+/+ and CLDN7−/− mouse kidneys. We found that deletion of CLDN7 increased the transepithelial resistance (TER) and decreased the paracellular permeability for Cl and Na+ in CLDN7−/− CD cells. Inhibition of transcellular Cl and Na+ channels has no significant effect on TER or dilution potentials. Current-voltage curves were linear in both CLDN7+/+ and CLDN7−/− CD cells, indicating that the ion flux was through the paracellular pathway. The impairment of Cl and Na+ permeability phenotype can be rescued by CLDN7 re-expression. We also found that WNK4 (its mutations lead to hypertension) expression, but not WNK1, was significantly increased in CLDN7−/− CD cell lines as well as in primary CLDN7−/− CD cells, suggesting that the expression of WNK4 was modulated by CLDN7. In addition, deletion of CLDN7 upregulated the expression level of the apical epithelial sodium channel (ENaC), indicating a potential cross-talk between paracellular and transcellular transport systems. This study demonstrates that CLDN7 plays an important role in salt balance in renal CD cells and modulating WNK4 and ENaC expression levels that are vital in controlling salt-sensitive hypertension. View Full-Text
Keywords: Claudin-7; tight junctions; permeability; WNK4; epithelial sodium channel (ENaC), collecting duct cells Claudin-7; tight junctions; permeability; WNK4; epithelial sodium channel (ENaC), collecting duct cells
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MDPI and ACS Style

Fan, J.; Tatum, R.; Hoggard, J.; Chen, Y.-H. Claudin-7 Modulates Cl and Na+ Homeostasis and WNK4 Expression in Renal Collecting Duct Cells. Int. J. Mol. Sci. 2019, 20, 3798.

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