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

Autor: Sassi, Ali, Wang, Yubao, Chassot, Alexandra, Komarynetz, Olga, Roth, Isabelle, Olivier, Valérie, Crambert, Gilles, Dizin, Eva, Boscardin, Emilie, Hummler, Edith, Eric, Féraille
Přispěvatelé: University of Geneva [Switzerland], National Center of Competence in Research Kidney Control of Homeostasis (Kidney.CH) [Zurich, Switzerland], Physiologie rénale et tubulopathies = Renal Physiology and tubulopathies [CRC], Centre National de la Recherche Scientifique (CNRS)-Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP), Université de Lausanne (UNIL)
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Zdroj: Journal of the American Society of Nephrology
Journal of the American Society of Nephrology, American Society of Nephrology, 2020, 31 (5), pp.1009-1023. ⟨10.1681/ASN.2019080790⟩
ISSN: 1046-6673
1533-3450
DOI: 10.1681/ASN.2019080790⟩
Popis: International audience; 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.
Databáze: OpenAIRE
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