Renal phosphate and vitamin D metabolism are regulated by proteohormone fibroblast growth factor 23 (FGF23), which is secreted by bone cells. FGF23 inhibits phosphate reabsorption and the production of calcitriol, active vitamin D (1,25(OH)D). FGF23 generated by other cells exerts further paracrine effects in the liver, heart, and immune system. The FGF23 plasma concentration is positively associated with the onset and progression of kidney and cardiovascular diseases, disclosing FGF23 as a potential disease biomarker. The effects of vitamin A on the expression of FGF23 are controversial. Vitamin A components, retinoids, are mainly effective through nuclear retinoic acid receptors (RAR) and exert different effects on bone. The aim of this study was to clarify whether vitamin A modulates the production of FGF23.
We studied the relevance of vitamin A for FGF23 production. Fgf23 transcripts were determined by real-time quantitative polymerase chain reaction in UMR106 osteoblast-like cells and IDG-SW3 osteocytes. FGF23 protein in the cell culture supernatant was measured by enzyme-linked immunosorbent assay.
All-trans-retinoic acid, retinyl acetate, RAR agonist TTNPB (4-[(E)-2-(5,6,7,8-Tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)-1-propenyl]benzoic acid), and 13-cis-retinoic acid downregulated the expression of the Fgf23 gene in a dose-dependent manner. This effect was significantly attenuated by RAR antagonist AGN193109 (4-[2-[5,6-Dihydro-5,5-dimethyl-8-(4-methylphenyl)-2-naphthalenyl]ethynyl]benzoic acid).
The present study demonstrated that vitamin A is a potent suppressor of FGF23 production through RAR.
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