Kidney Week

Abstract: FR-PO504

1,25-Dihydroxyvitamin D Stimulation Increases FGF23 Expression in Calcified Vessels Under High Phosphate Condition

Session Information

• Bone and Mineral Metabolism: Basic
  October 26, 2018 | Location: Exhibit Hall, San Diego Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Bone and Mineral Metabolism

• 401 Bone and Mineral Metabolism: Basic

Authors

• Ohya, Masaki, Wakayama Medical University, Wakayama, Japan

Masaki Ohya,

• Kawakami, Kazuki, Wakayama Medical University, Wakayama, Japan

Kazuki Kawakami,

• Sonou, Tomohiro, Wakayama Medical University, Wakayama, Japan

Tomohiro Sonou,

• Yashiro, Mitsuru, Wakayama Medical University, Wakayama, Japan

Mitsuru Yashiro,

• Mima, Toru, Wakayama Medical University, Wakayama, Japan

Toru Mima,

• Negi, Shigeo, Wakayama Medical University, Wakayama, Japan

Shigeo Negi,

• Shigematsu, Takashi, Wakayama Medical University, Wakayama, Japan

Takashi Shigematsu,

Background

Elevated fibroblast growth factor 23 (FGF23) is observed in patients with end stage renal disease (ESRD) or chronic kidney disease (CKD). Vascular calcification is also a commonly observed in patients with ESRD or CKD, which leads to increased cardiovascular events and mortality. Expression of FGF23 in bone is elevated by the factors as serum Pi, parathyroid hormone (PTH), and 1,25-Dihydroxyvitamin D, and is suppressed by dentin matrix protein-1 (DMP1). We hypothesized that 1,25-Dihydroxyvitamin D stimulates FGF23 expression in Pi-induced calcified vessels.

Methods

We performed aortic tissue culture in the medium with normal phosphate (0.9mM), high P (3.8mM)i, and high Pi with 1,25Dihydroxyvitamin D (1,25D) for 10 days, subsequently von kossa staining, quantification of calcium contents and gene expression of Fgf23, Dmp1, and other osteocyte/osteoblast marker; alkaline phosphatase (Alp), dickkopf-related protein 1 (Dkk1), and screlostin, and immunostaining of FGF23 and DMP1 in the cultured aorta.

Results

Aortic ring cultured in the medium with high Pi and high Pi+1,25D showed calcium deposition and increased calcium contents significantly. Quantitative PCR demonstrated that increasedAlpand Dkk1expression and unchanged Sost expression in high Pi+1,25D medium. Expression of FGF23 in aorta ring is not altered under the high Pi condition, but is increased under the high Pi+1,25D condition. DMP1 expression in aorta is increased under the high Pi condition while the up-regulation is attenuated under the high Pi+1,25D condition.

Conclusion

These results suggest that 1,25Dihydroxyvitamin stimulation increases FGF23 expression in calcified vessels under high phosphate condition.

A. Quantification of Fgf23gene expression. B. Immunoblot image of FGF23 protein. C. Immunohistochmical images of FGF23 expression. Normal Pi; 0.9 mmol/L phosphate, High Pi; 3.8 mmol/L phosphate, High Pi+1.25D; 3.8 mmol/L phosphate and 100 nmol/L 1,25-Dihydroxyvitamin D_3.

Funding

• Government Support - Non-U.S.