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Interaction between Epithelial Sodium Channel γ -Subunit and Claudin-8 Modulates Paracellular Sodium Permeability in Renal Collecting Duct

Abstract : Background: Water and solute transport across epithelia can occur via the transcellular or paracellular pathways. Tight junctions play a key role in mediating paracellular ion reabsorption in the kidney. In the renal collecting duct, which is a typical absorptive tight epithelium, coordination between transcellular sodium reabsorption and paracellular permeability may prevent the backflow of reabsorbed sodium to the tubular lumen along a steep electrochemical gradient. Methods: To investigate whether transcellular sodium transport controls tight-junction composition and paracellular permeability via modulating expression of the transmembrane protein claudin-8, we used cultured mouse cortical collecting duct cells to see how overexpression or silencing of epithelial sodium channel (ENaC) subunits and claudin-8 affect paracellular permeability. We also used conditional kidney tubule-specific knockout mice lacking ENaC subunits to assess the ENaC's effect on claudin-8 expression. Results: Overexpression or silencing of the ENaC γ-subunit was associated with parallel and specific changes in claudin-8 abundance. Increased claudin-8 abundance was associated with a reduction in paracellular permeability to sodium, whereas decreased claudin-8 abundance was associated with the opposite effect. Claudin-8 overexpression and silencing reproduced these functional effects on paracellular ion permeability. Conditional kidney tubule-specific ENaC γ-subunit knockout mice displayed decreased claudin-8 expression, confirming the cell culture experiments' findings. Importantly, ENaC β-subunit or α-subunit silencing or kidney tubule-specific β-ENaC or α-ENaC knockout mice did not alter claudin-8 abundance. Conclusions: Our data reveal the specific coupling between ENaC γ-subunit and claudin-8 expression. This coupling may play an important role in preventing the backflow of reabsorbed solutes and water to the tubular lumen, as well as in coupling paracellular and transcellular sodium permeability.
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https://www.hal.inserm.fr/inserm-03033250
Contributor : Gilles Crambert <>
Submitted on : Tuesday, December 1, 2020 - 11:50:50 AM
Last modification on : Wednesday, June 2, 2021 - 4:26:37 PM
Long-term archiving on: : Tuesday, March 2, 2021 - 6:58:36 PM

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Ali Sassi, Yubao Wang, Alexandra Chassot, Olga Komarynetz, Isabelle Roth, et al.. Interaction between Epithelial Sodium Channel γ -Subunit and Claudin-8 Modulates Paracellular Sodium Permeability in Renal Collecting Duct. Journal of the American Society of Nephrology, American Society of Nephrology, 2020, 31 (5), pp.1009-1023. ⟨10.1681/ASN.2019080790⟩. ⟨inserm-03033250⟩

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