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

ECU Author/Contributor (non-ECU co-authors, if there are any, appear on document)

Yan-Hua Chen (Creator)

Junming Fan (Creator)

John Hoggard (Creator)

Rodney Tatum (Creator)

Institution

East Carolina University (ECU )

Web Site: http://www.ecu.edu/lib/

Abstract: Claudin-7 knockout (CLDN7-/-) mice display renal salt wasting and dehydration\r\nphenotypes. To address the role of CLDN7 in kidneys, we established collecting duct (CD) cell\r\nlines from CLDN7+/+ and CLDN7-/- mouse kidneys. We found that deletion of CLDN7 increased\r\nthe transepithelial resistance (TER) and decreased the paracellular permeability for Cl- and Na+ in\r\nCLDN7-/- CD cells. Inhibition of transcellular Cl- and Na+ channels has no significant effect on TER\r\nor dilution potentials. Current-voltage curves were linear in both CLDN7+/+ and CLDN7-/- CD cells,\r\nindicating that the ion flux was through the paracellular pathway. The impairment of Cl- and Na+\r\npermeability phenotype can be rescued by CLDN7 re-expression. We also found that WNK4 (its\r\nmutations lead to hypertension) expression, but not WNK1, was significantly increased in CLDN7-/-\r\nCD cell lines as well as in primary CLDN7-/- CD cells, suggesting that the expression of WNK4\r\nwas modulated by CLDN7. In addition, deletion of CLDN7 upregulated the expression level of the\r\napical epithelial sodium channel (ENaC), indicating a potential cross-talk between paracellular and\r\ntranscellular transport systems. This study demonstrates that CLDN7 plays an important role in\r\nsalt balance in renal CD cells and modulating WNK4 and ENaC expression levels that are vital in\r\ncontrolling salt-sensitive hypertension.

Additional Information

Publication

Other

Language: English

Date: 2023

Subjects

Claudin-7\; tight junctions\; permeability\; WNK4\; epithelial sodium channel (ENaC), collecting duct cells

Email this document to