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

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    Author
    Fan, Junming; Tatum, Rodney; Hoggard, John; Chen, Yan-Hua
    Abstract
    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.
    URI
    http://hdl.handle.net/10342/7979
    Subject
    Claudin-7; tight junctions; permeability; WNK4; epithelial sodium channel (ENaC), collecting duct cells
    Date
    2019-07-30
    Citation:
    APA:
    Fan, Junming, & Tatum, Rodney, & Hoggard, John, & Chen, Yan-Hua. (July 2019). Claudin-7 Modulates Cl− and Na+ Homeostasis and WNK4 Expression in Renal Collecting Duct Cells. International Journal of Molecular Sciences, (20:15), p.. Retrieved from http://hdl.handle.net/10342/7979

    Display/Hide MLA, Chicago and APA citation formats.

    MLA:
    Fan, Junming, and Tatum, Rodney, and Hoggard, John, and Chen, Yan-Hua. "Claudin-7 Modulates Cl− and Na+ Homeostasis and WNK4 Expression in Renal Collecting Duct Cells". International Journal of Molecular Sciences. 20:15. (.), July 2019. March 04, 2021. http://hdl.handle.net/10342/7979.
    Chicago:
    Fan, Junming and Tatum, Rodney and Hoggard, John and Chen, Yan-Hua, "Claudin-7 Modulates Cl− and Na+ Homeostasis and WNK4 Expression in Renal Collecting Duct Cells," International Journal of Molecular Sciences 20, no. 15 (July 2019), http://hdl.handle.net/10342/7979 (accessed March 04, 2021).
    AMA:
    Fan, Junming, Tatum, Rodney, Hoggard, John, Chen, Yan-Hua. Claudin-7 Modulates Cl− and Na+ Homeostasis and WNK4 Expression in Renal Collecting Duct Cells. International Journal of Molecular Sciences. July 2019; 20(15) . http://hdl.handle.net/10342/7979. Accessed March 04, 2021.
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