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Abstract: TH-OR48

Regulation of Sodium Excretion and Blood Pressure by the Nuclear Factor of Activated T Cells 5 (NFAT5) in Renal Tubular Cells

Session Information

Category: Hypertension and CVD

  • 1403 Hypertension and CVD: Mechanisms

Authors

  • Hiramatsu, Akiko, Department of Nephrology, Kumamoto University, Graduate School of Medical Sciences, Kumamoto, Japan
  • Izumi, Yuichiro, Department of Nephrology, Kumamoto University, Graduate School of Medical Sciences, Kumamoto, Japan
  • Kakizoe, Yutaka, Department of Nephrology, Kumamoto University, Graduate School of Medical Sciences, Kumamoto, Japan
  • Adachi, Masataka, Department of Nephrology, Kumamoto University, Graduate School of Medical Sciences, Kumamoto, Japan
  • Nonoguchi, Hiroshi, Department of Nephrology, Kumamoto University, Graduate School of Medical Sciences, Kumamoto, Japan
  • Kuwabara, Takashige, Department of Nephrology, Kumamoto University, Graduate School of Medical Sciences, Kumamoto, Japan
  • Mukoyama, Masashi, Department of Nephrology, Kumamoto University, Graduate School of Medical Sciences, Kumamoto, Japan
Background

NFAT5 is an osmoprotective transcription factor, which is crucial for cell survival under hypertonic conditions such as those encountered in the renal medulla. Physiological role of NFAT5 in the kidney, however, is still obscure. We investigated the role of NFAT5 in renal tubules using renal tubular cell-specific NFAT5-knockout (KO) mice.

Methods

We crossed NFAT5 floxed mice with Pax8-rtTA/LC-1 mice to obtain mice with inducible and specific deletion of NFAT5 in renal tubular cells. To characterize the mice, urine and blood parameters and blood pressure of wild type (WT) and KO mice were examined at basal condition. Then, WT mice and KO mice were fed either a high-salt diet (HSD) or a regular-salt diet (RSD) for 4 weeks. The mRNA expression of sodium transporter-related genes in the kidney was examined by real-time PCR. Protein expression of the epithelial sodium channel (ENaC) in the membrane fraction was examined by Western blotting. Concentrations of urea and sodium in the renal medulla were measured.

Results

Compared to WT mice, KO mice exhibited polyuria (WT vs. KO: 2.0 ± 0.08 vs. 5.2 ± 0.18 ml/day) at basal condition. The serum sodium level was increased (151.8 ± 0.78 vs. 156.6 ± 0.45 mEq/L) and the urinary sodium excretion was decreased (498.7 ± 25 vs. 368.9 ± 15 mEq/gCr) in KO mice. Interestingly, the systolic blood pressure was significantly elevated in KO mice (97.4 ± 2.4 vs.114.9 ± 1.1 mmHg). mRNA expressions of AQP2 and UT-A1, a water channel and a urea transporter, respectively, were significantly decreased, while the expressions of ENaC were increased in KO mice. There was no significant difference in the plasma renin activity or aldosterone levels. The systolic blood pressure of KO mice fed HSD was significantly elevated earlier compared to WT mice fed HSD. ENaC protein levels were increased in KO mice fed HSD compared to WT. The urea concentration was lower and the Na concentration was higher in the medulla of KO mice than those of WT mice. HSD significantly increased the medullary Na concentration, but not the urea concentration in KO mice.

Conclusion

These results suggest that NFAT5 can regulate the urine concentration and sodium reabsorption in renal tubules, which could be important for body fluid homeostasis and blood pressure regulation.

Funding

  • Government Support – Non-U.S.