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Kidney Week

Abstract: PO0609

Involvement of Calcium-Sensing Receptor in the Development of Interstitial Fibrosis

Session Information

  • CKD Mechanisms - 1
    October 22, 2020 | Location: On-Demand
    Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

  • 2103 CKD (Non-Dialysis): Mechanisms

Authors

  • Kurosawa, Akira, Department of Nephrology and Hypertension, Saitama Medical Center, Saitama Medical University, Kawagoe, Saitama, Japan
  • Takayanagi, Kaori, Department of Nephrology and Hypertension, Saitama Medical Center, Saitama Medical University, Kawagoe, Saitama, Japan
  • Shimizu, Taisuke, Department of Nephrology and Hypertension, Saitama Medical Center, Saitama Medical University, Kawagoe, Saitama, Japan
  • Terao, Masaaki, Department of Nephrology and Hypertension, Saitama Medical Center, Saitama Medical University, Kawagoe, Saitama, Japan
  • Hara, Hiroaki, Department of Nephrology and Hypertension, Saitama Medical Center, Saitama Medical University, Kawagoe, Saitama, Japan
  • Iwashita, Takatsugu, Department of Nephrology and Hypertension, Saitama Medical Center, Saitama Medical University, Kawagoe, Saitama, Japan
  • Hasegawa, Hajime, Department of Nephrology and Hypertension, Saitama Medical Center, Saitama Medical University, Kawagoe, Saitama, Japan
Background

Physiological and pathophysiological role of renal Ca sensing receptor (CaSR) have not been well understood. We have reported the down regulation of CaSR in the process of renal interstitial fibrogenesis along with the down regulation of Mg transporting molecules, suggesting that CaSR plays an important role in the development of renal damage associated with Mg deficiency. We report here an analysis of the effects of calcimimetics administration on renal fibrosis models.

Methods

The left ureters of 8-week-old SD rat were ligated to create unilateral ureter obstruction (UUO) models and studied after 7 days. Cinacalcet 1.0 mg/day, a calcimimetics, was administered to a part of UUO animals. Experiments were performed in three groups of sham group, UUO group and UUO+Cinacalcet group (n=5). Fibrosis was evaluated by Azan staining and analysis of mRNAs of fibrosis-related molecules. We also studied on mRNA expression of Mg-transporting molecules.

Results

It was confirmed from immunohistochemistry and gene expression that CaSR expression was remarkably decreased by UUO (RT-PCR: sham 1.01±0.09 vs UUO 0.04±0.00, n=5).
Cinacalcet treatment partially restored the expression by approximately 50% compared to UUO group. In Azan staining, an increase in the fibrosis area and a recrease in the non-damaged tubules were apparent in UUO, however, Cinacalcet treatment partially rescued.
mRNA expression of TGF-beta and MCP-1 was not significantly decreased by Cinacalcet treatment as compared to UUO group. mRNA expression of claudin-14, 16 and 19, Mg transpirting molecules, seemed to be increased by Cinacalcet treatment, however, it was not statistically significant. However, Cinacalcet partially, but significantly increased the mRNA expression of TRPM6 comparing to UUO group (sham: 1.01±0.07, UUO: 0.35±0.01, Cinacalcet: 0.41±0.02).

Conclusion

The expression of claudin-16 and TRPM6 was significantly decreased with the development of fibrosis in UUO. The effect of CaSR activation and upregulation by Cinacalcet was limited, however, it restored the progression of fibrosis and impairment of Mg reabsorption. CaSR may play a key role for the Mg loss-relating renal fibrogenesis.