Impact of Annexin A 7 Deficiency on FGF23 Plasma Concentrations

Abstract

Background/Aims: The release of fibroblast growth factor FGF23, a powerful regulator of 1,25(OH)₂D₃ formation and mineral metabolism, is stimulated by store-operated Ca²⁺ entry (SOCE), which is accomplished by the pore forming Ca²⁺ release activated channel protein Orai1. Regulators of Orai1 and thus FGF23 release include serum & glucocorticoid inducible kinase SGK1, a kinase up-regulated by glucocorticosteroids. Some effects of glucocorticoids require the presence of annexin A7, such as suppression of prostaglandin E2 in gastric glands. The present study thus explored whether annexin A7 impacts on FGF23 plasma levels. Methods: Comparisons were made between gene targeted mice lacking functional annexin A7 (Anx7^-/-) and their wild type littermates (Anx7^+/+). Serum C-terminal-FGF23, intact FGF23, 1,25(OH)₂D₃ and PTH concentrations were measured by ELISA or EIA. The serum and urinary phosphate concentrations were measured by colorimetry, the serum Ca²⁺ concentration and the urinary Ca²⁺ concentration by flame photometry. Results: Serum C-terminal FGF23 levels and corticosterone levels were significantly higher and serum 1,25(OH)₂ D₃ and PTH levels were significantly lower in Anx7^-/- than in Anx7^+/+ mice. Water intake was slightly but significantly higher in Anx7^-/- mice than in Anx7^+/+ mice. No significant difference was observed between Anx7^-/- and Anx7^+/+ mice in urinary fluid excretion, plasma Ca²⁺ concentration, plasma phosphate concentration and urinary Ca²⁺ output. The urinary phosphate output was significantly lower in Anx7^-/- mice than in Anx7^+/+ mice. Conclusion: Annexin A7 deficiency upregulates FGF23 plasma levels, an effect paralleled by increased corticosterone plasma levels, as well as decreased 1,25(OH)₂ D₃ and PTH plasma levels.