Department of Physiology, University of Hohenheim, Stuttgart, Germany.
Department of Physiology, University of Hohenheim, Stuttgart, Germany.
Nutrition. 2020 Nov-Dec;79-80:110988. doi: 10.1016/j.nut.2020.110988. Epub 2020 Aug 28.
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.
肾磷酸盐和维生素 D 代谢受蛋白激素成纤维细胞生长因子 23（FGF23）调节，其由骨细胞分泌。FGF23 抑制磷酸盐重吸收和活性维生素 D（1,25（OH）D）的生成。由其他细胞产生的 FGF23 在肝脏、心脏和免疫系统中发挥进一步的旁分泌作用。FGF23 的血浆浓度与肾脏和心血管疾病的发生和进展呈正相关，表明 FGF23 是一种潜在的疾病生物标志物。维生素 A 对 FGF23 表达的影响存在争议。维生素 A 成分视黄醇主要通过核视黄酸受体（RAR）发挥作用，并对骨骼产生不同的影响。本研究旨在阐明维生素 A 是否调节 FGF23 的产生。
我们研究了维生素 A 与 FGF23 产生的相关性。在 UMR106 成骨样细胞和 IDG-SW3 成骨细胞中通过实时定量聚合酶链反应确定 Fgf23 转录物。通过酶联免疫吸附试验测定细胞培养上清液中的 FGF23 蛋白。
全反式视黄酸、视黄酯、RAR 激动剂 TTNPB（4-[(E)-2-（5,6,7,8-四氢-5,5,8,8-四甲基-2-萘基）-1-丙烯基]苯甲酸）和 13-顺式视黄酸以剂量依赖性方式下调 Fgf23 基因的表达。这种作用被 RAR 拮抗剂 AGN193109（4-[2-[5,6-二氢-5,5-二甲基-8-（4-甲基苯基）-2-萘基]乙炔基]苯甲酸）显著减弱。
本研究表明，维生素 A 通过 RAR 是 FGF23 产生的有效抑制剂。
