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Abstract: TH-PO428

Calciprotein Particle Contributes to the Synthesis and Secretion of Fibroblast Growth Factor 23 Induced by Dietary Phosphate Intake

Session Information

Category: Nutrition, Inflammation, and Metabolism

  • 1401 Nutrition, Inflammation, Metabolism

Author

  • Akiyama, Kenichi, Tokyo Women's Medical University, Tokyo, Japan
Background

It has been reported that the synthesis and secretion of fibroblast growth factor 23 (FGF23) induced by phosphate also require calcium. However this mechanism is still unclear. Highly concentrated phosphate and calcium are crystallized and formed calciprotein particle (CPP) with some proteins including fetuin-A in extracellular fluid. CPP is considered the pathogenesis of some complications such as an inflammatory response in chronic kidney disease. The role of CPP on the synthesis and secretion of FGF23 was investigated.

Methods

Rat osteoblastic cell line (UMR-106 cell) was treated by various dose of phosphate or artificially made CPP for 4 and 24 hours. Protein level of FGF23 in the medium and mRNA expression level of FGF23 were analyzed. Serum phosphate, FGF23 and CPP levels and FGF23 mRNA expression level in cranial bone were also evaluated in C57BL/6J mice 2 and 6 hours after phosphate administration using a feeding tube and 10 days after switching to the high phosphate diet.

Results

Both phosphate and artificial CPP treatments for 4 and 24 hours significantly increased FGF23 protein level in the medium of UMR-106 cell at dose-dependent manner. The upregulation of FGF23 mRNA expression level was observed only 24 hours after both treatments. The supplementation of citrate as an inhibitor of CPP formation canceled all of these findings. The significant increases of serum CPP and serum FGF23 levels compared with control treatment were observed 2 and 6 hours, respectively after the gavage of phosphate. However FGF23 mRNA expression level in cranial bone did not change in these mice. Significant increases of serum phosphate, CPP and FGF23 levels and upregulation of FGF23 mRNA expression level in cranial bone were confirmed in mice fed high phosphate diet for 10 days.

Conclusion

These findings suggest CPP but not phosphate itself might be contributing to the dietary phosphate-induced both postprandial secretion and sustained high level of serum FGF23 level.