Claudin-7 Modulates Cl− and Na+ Homeostasis and WNK4 Expression in Renal Collecting Duct Cells
Fan, Junming; Tatum, Rodney; Hoggard, John; Chen, Yan-Hua
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.
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. , (), - . Retrieved from http://hdl.handle.net/10342/7979
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". . . (), July 2019. September 24, 2023. http://hdl.handle.net/10342/7979.
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," , no. (July 2019), http://hdl.handle.net/10342/7979 (accessed September 24, 2023).
Fan, Junming, Tatum, Rodney, Hoggard, John, Chen, Yan-Hua. Claudin-7 Modulates Cl− and Na+ Homeostasis and WNK4 Expression in Renal Collecting Duct Cells. . July 2019; (): . http://hdl.handle.net/10342/7979. Accessed September 24, 2023.