Abstract: FR-PO1092
Possible Involvement of Renal Tubular NFAT5 in Aging-Associated Renal Phenotypes and Dysfunction
Session Information
- CKD Mechanisms: Progression, Fibrosis, and Beyond
November 03, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: CKD (Non-Dialysis)
- 2303 CKD (Non-Dialysis): Mechanisms
Authors
- Maruyama, Kosuke, Department of Nephrology, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Kumamoto, Japan
- Izumi, Yuichiro, Department of Nephrology, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Kumamoto, Japan
- Ono, Makoto, Department of Nephrology, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Kumamoto, Japan
- Kakizoe, Yutaka, Department of Nephrology, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Kumamoto, Japan
- Kuwabara, Takashige, Department of Nephrology, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Kumamoto, Japan
- Mukoyama, Masashi, Department of Nephrology, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Kumamoto, Japan
Background
The number of patients with chronic kidney disease (CKD) and hypertension is increased with age; however, it is not clearly defined why and how aging causes renal dysfunction and hypertension. Nuclear factor of activated T-cells 5 (NFAT5) is a transcription factor that is activated upon hypertonic conditions as observed in the renal medulla. We have already shown that the renal tubular cell-specific NFAT5 conditional knockout (KO) mice exhibit salt-sensitive hypertension, while the mice exhibit impaired urine concentrating ability and are susceptible to renal fibrosis. These phenotypes resemble aging-associated renal dysfunction, i.e., urine concentrating disorder, salt-sensitive hypertension, and renal fibrosis. We therefore investigated the possible involvement of NFAT5 in aging-related changes of the kidney.
Methods
The mRNA expressions of NFAT5 and its downstream genes including AQP2, urea transporter A-1 (UTA-1), and aldose reductase (AR) were examined by real-time PCR in the whole kidney tissue of wild type (WT) mice at 3, 6, 12, and 18 months old. To investigate the involvement of NFAT5 in aging-related phenotypes of the kidney, kidneys collected from NFAT5 KO mice (3 and 18 months old) were characterized and compared with WT mice. Senescence-associated beta-galactosidase (SA-β-Gal) activity was examined by fluorescence study in the whole kidney slices. Gene expressions of senescence-associated secretory phenotype (SASP)-related factors (TGF-β1, COL1A1, ICAM1, PAI-1, and MMP3) were examined by real-time PCR. Renal fibrosis was evaluated by AZAN staining.
Results
While the expression of NFAT5 was increased with age, the mRNA expressions of AQP2, UTA-1 and AR were decreased significantly at 6 and 12 months old compared to 3 months old. SA-β-Gal activity was increased in the corticomedullary region in KO mice at 3 months. Gene expressions of SASP-related factors were significantly increased in KO mice. At 18 months old, KO mice exhibited renal atrophy and fibrosis in the medulla, which phenotypes were significantly accelerated than WT mice.
Conclusion
These results indicate that the expression of genes downstream of NFAT5 could be decreased with aging kidney, suggesting that the decreased activity of NFAT5 may be involved in aging-related renal dysfunction.