Low‐Salt Diet Induces Claudin‐3 Expression and Drives Adaptive Changes in Collecting Duct of Claudin‐3‐Deficient Mice

Article Article scientifique Article Low‐Salt Diet Induces Claudin‐3 Expression and Drives Adaptive Changes in Collecting Duct of Claudin‐3‐Deficient Mice eng 2026-04-03 2026-05 author Sassi Ali 0000-0002-3194-777X Department of Cellular Physiology and Metabolism, Faculty of Medicine, University of Geneva, Geneva, Switzerland. 882466 Département de physiologie cellulaire et métabolisme (PHYME) author Chassot Alexandra Department of Cellular Physiology and Metabolism, Faculty of Medicine, University of Geneva, Geneva, Switzerland. 583119 Département de physiologie cellulaire et métabolisme (PHYME) author Jellali Sara Department of Cellular Physiology and Metabolism, Faculty of Medicine, University of Geneva, Geneva, Switzerland. 400139 author Liaudet Nicolas 0000-0002-0749-5857 Bioimaging Core Facility, Faculty of Medicine, University of Geneva, Geneva, Switzerland. 862067 Services communs de la faculté de médecine (SCMU) author Polat Ana Elif Department of Cellular Physiology and Metabolism, Faculty of Medicine, University of Geneva, Geneva, Switzerland. 400753 author Baier Felix Visceral Surgery and Medicine, Inselspital, Bern University Hospital, Department for BioMedical Research, University of Bern, Bern, Switzerland. author Stroka Deborah Visceral Surgery and Medicine, Inselspital, Bern University Hospital, Department for BioMedical Research, University of Bern, Bern, Switzerland. author Furuse Mikio Division of Cell Structure, National Institute for Physiological Sciences, Okazaki, Japan. author Feraille Eric Department of Cellular Physiology and Metabolism, Faculty of Medicine, University of Geneva, Geneva, Switzerland. 27356 Département de physiologie cellulaire et métabolisme (PHYME) e70216 10.1111/apha.70216 41930611 1748-1708 PMC13047526 Aim: Renal sodium reabsorption occurs through both transcellular and paracellular pathways. Tight junction proteins play a key role in mediating paracellular transport. The collecting duct is critical for the fine tuning of sodium balance and is highly responsive to changes in dietary salt intake. This study aimed to determine whether a low-sodium diet modulates paracellular sodium permeability by regulating the expression or localization of claudin-3, a major tight junction protein in the collecting duct. Methods: Wild-type and claudin-3 knockout male mice were fed low (0.01%) or normal (0.18%) sodium diets for 7 days, with or without treatment with spironolactone, a mineralocorticoid receptor antagonist. The expression of tight junction proteins was analyzed by immunoblotting and immunofluorescence. Functional effects of claudin-3 on ion permeability were evaluated in cultured mouse collecting duct principal cells using chamber recordings after claudin-3 overexpression or gene silencing. Results: Low-sodium diet increases claudin-3 expression in mouse kidneys. In cultured cells, aldosterone enhanced claudin-3 abundance and its plasma membrane localization. Claudin-3 overexpression reduced, while its silencing increased paracellular permeability to sodium and chloride. Claudin-3 knockout mice on a low-sodium diet compensated by upregulating epithelial sodium channel subunits, claudin-4, claudin-8, and claudin-10. This adaptive response persisted under mineralocorticoid receptor blockade. Conclusions: Our findings demonstrate that aldosterone strengthens the paracellular sodium barrier in the collecting duct by inducing claudin-3. In the absence of claudin-3, compensatory regulation of other claudins and sodium transporters preserves sodium homeostasis under low-salt conditions, thus revealing adaptive mechanisms in renal sodium handling. Aldosterone Claudin‐3 Collecting duct Kidney Low‐salt diet Sodium transport Dewey 612 Swiss National Science Foundation Cell autonomous mechanisms of control of sodium transport in renal collecting duct 156736 CH Swiss National Science Foundation Modulation of kidney tubule paracellular permeability in health and disease 207441 CH 134 Département de physiologie cellulaire et métabolisme 21C false 20 Laboratoire de physiologie et pathophysiologie des cellules rénales 29 Acta physiologica 242 5 579e025c-a61f-4a9a-9d08-2300647b5279 Article (Published version) Public file.pdf 9826587 application/pdf CC BY-4.0 c4a02e3668e636e40ce74845e94f0232f53eeaaf5d4505e396690375e81827e4 ba78d47e-b42b-4629-81c2-e8898e2b8fbc Supplemental data Public apha70216-sup-0001-figures.pdf 542620 application/pdf 4033285841c4330f63a89011737adff9f2d4d294fcf5382fd62dbc6f636c6964 openAccess Faculté de médecine / Section de médecine fondamentale / Département de physiologie cellulaire et métabolisme

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Low‐Salt Diet Induces Claudin‐3 Expression and Drives Adaptive Changes in Collecting Duct of Claudin‐3‐Deficient Mice	Acta physiologica			2026	4	21

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Jellali, Sara