Aldosterone Upregulates Tight Junction Expression of Claudin-4, Decreasing Paracellular Na+ Permeability in the Renal Cortical Collecting Duct

Under conditions of low dietary salt intake, plasma aldosterone levels are upregulated, increasing Na+ reabsorption in the renal cortical collecting duct (CCD). While aldosterone is known to enhance transcellular Na+ reabsorption, its effect on paracellular transport remains unknown. Paracellular transport is mediated by tight junction (TJ) proteins called claudins. We used a murine CCD cell line, mpKCCD c14, to study the effect of aldosterone on paracellular transport. We found that aldosterone significantly increased transepithelial resistance (TER) and decreased paracellular Na+ permeability (PNa), when transcellular transport is blocked. We also found that aldosterone increased TJ expression of a Na+ barrier claudin, claudin-4, suggesting that increased claudin-4 expression at the TJ is responsible for the decrease in PNa. To confirm this, we stably knocked–down claudin-4 expression using shRNAs. This diminished both baseline TER and aldosterone-induced increases in TER, and PCl/PNa. Aldosterone is kn...