Abstract: FR-PO576
Claudin-3: Physiological Role in Renal Cortical Collecting Duct
Session Information
- Fluid, Electrolyte, and Acid-Base Disorders: Basic
October 25, 2024 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Fluid, Electrolytes, and Acid-Base Disorders
- 1101 Fluid, Electrolyte, and Acid-Base Disorders: Basic
Authors
- Charlemagne, Thibaut, Department of Cellular Physiology and Metabolism, Faculty of Medicine, Geneva, Switzerland
- Chassot, Alexandra, Department of Cellular Physiology and Metabolism, Faculty of Medicine, Geneva, Switzerland
- Feraille, Eric, Department of Cellular Physiology and Metabolism, Faculty of Medicine, Geneva, Switzerland
- Sassi, Ali, Department of Cellular Physiology and Metabolism, Faculty of Medicine, Geneva, Switzerland
Group or Team Name
- Eric Feraille's Group.
Background
In the kidney, ion and fluid 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. The renal collecting duct (CD) is the place of fine tuning of Na+ reabsorption and it is mainly regulated by aldosterone. Aldosterone classically regulates Na+ transport through the transcellular pathway. We hypothesized that aldosterone modulates also the paracellular pathway. Paracellular ion permeability is mainly dependent on tight junction permeability. Claudin-3 is one of the main tight junction proteins expressed along the CD.
Methods
We used cultured mouse CD principal cells (mCCD) and mouse models to study the effects of aldosterone on claudin-3. Overexpression and silencing of claudin-3 were used to assess the paracellular permeability of claudin-3. WT and claudin-3 knockout male mice were fed for 7 days with either low (0.01 %), normal (0.18 % ) or high sodium (1.25 %) diet. One group of mice fed a low sodium diet received 0.35 mg/100g body wt/day of spironolactone for 7 days.
Results
We showed that aldosterone increased protein levels of claudin-3 in cultured CD principal cells. Overexpression of claudin-3 was associated with a reduction in paracellular permeability to sodium and chloride, whereas silencing of claudin-3 was associated with the opposite effect. We also showed that a low-salt diet, which stimulated aldosterone secretion, was associated with increased claudin-3 abundance in the mouse kidney. Reciprocally, mice treated with spironolactone, a mineralocorticoid receptor antagonist, displayed decreased claudin-3 expression. Importantly, claudin-3 knockout mice displayed increased γ-ENaC and claudin-4 protein abundance under low-salt diet compared to WT mice.
Conclusion
Our results show that aldosterone modulates the expression of claudin-3 and that claudin-3 acts as paracellular NaCl barrier. We also show a specific adaptation of clausin-3 deficient mice to low-salt diet. Claudin-3 may then play an important role in preventing the backflow of reabsorbed NaCl.