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Kidney Week

Abstract: TH-PO476

Investigation of the Role of Renal Tubular NFAT5 in Renal Fibrogenesis Caused by Unilateral Ureteral Obstruction

Session Information

  • CKD: Mechanisms - I
    November 07, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
    Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

  • 2103 CKD (Non-Dialysis): Mechanisms

Authors

  • Ono, Makoto, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan
  • Matsuo, Naomi, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan
  • Izumi, Yuichiro, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan
  • Eguchi, Koji, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan
  • Hiramatsu, Akiko, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan
  • Nakayama, Yushi, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan
  • Inoue, Hideki, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan
  • Kakizoe, Yutaka, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan
  • Kuwabara, Takashige, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan
  • Mukoyama, Masashi, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan
Background

NFAT5 (nuclear factor of activated T-cells 5) is a transcription factor that stimulates the expression of osmoprotective genes in response to extracellular hypertonicity, contributing to cell survival even in extreme hypertonic conditions. Not only hypertonicity but also hypoxia, oxidative stress, and toll-like receptor signaling, which promote fibrogenesis in the kidney, have been suggested to increase the NFAT5 activity. In the present study, we investigated the role of NFAT5 in renal fibrogenesis using renal tubular cell-specific NFAT5 conditional knockout (cKO) mice.

Methods

We generated renal tubular cell-specific NFAT5 cKO mice by crossing NFAT5 floxed mice with Pax8-rtTA/LC-1 mice, in which Cre recombinase was specifically expressed in renal tubular cells by the treatment with doxycycline. Wild-type (WT) mice and NFAT5 cKO mice were subjected to unilateral ureteral obstruction (UUO) or sham-operation. After 7 days, mice were sacrificed and kidneys were collected for analysis. The mRNA expression levels of NFAT5 and markers for fibrogenesis (TGF-β, α-SMA, CCL2, Col1, Col3, KIM-1, NGAL) in the kidney were examined by real-time PCR. Renal fibrosis was evaluated by Azan staining.

Results

In WT mice, the expression of NFAT5 mRNA was two times greater in the kidney from UUO mice than that from sham-operated mice. Fibrogenesis-related mRNAs were significantly increased in the kidney from UUO mice compared with that from sham-operated mice. In the UUO groups, the expressions of NGAL, TGF-β and collagen 3α1 tended to be higher in the kidney from NFAT5 cKO mice compared with that from WT mice. Azan staining showed a progression of fibrosis in the kidney from NFAT5 cKO mice.

Conclusion

NFAT5 in renal tubular cells may contribute to protective action against the development of renal fibrosis caused by UUO.