Regulation of phosphate homeostasis by PTH, vitamin D, and FGF23.
Regulation of phosphate homeostasis by PTH, vitamin D, and FGF23.
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DOI：
10.1146/annurev.med.051308.111339
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发表时间：
2010
影响因子：
10.5
通讯作者：
Jüppner H
中科院分区：
文献类型：
--
作者：
Bergwitz C;Jüppner H
在过去的几十年中，钙稳态的调节已被广泛研究，相对较少的是了解磷酸盐稳态的调节。成纤维细胞生长因子23（FGF 23）是以前未认识到的激素骨-甲状旁腺-肾轴的一部分，其由PTH、1，25（OH）2-维生素D（1，25（OH）2D）、饮食和血清磷水平调节。骨细胞合成和分泌FGF 23受1，25（OH）2D和血清磷的正调控，受与X染色体上的内肽酶（PHEX）同源的磷酸盐调节基因和牙本质基质蛋白1（DMP 1）的负调控，其机制尚不清楚。反过来，FGF 23抑制1，25（OH）2D的合成，并且它可以负调节甲状旁腺分泌甲状旁腺激素（PTH）。然而，FGF 23与PTH协同作用，通过减少近端小管中肾钠-磷酸盐共转运蛋白NaPi-IIa和NaPi-IIc的表达来增加肾磷酸盐排泄。这些因素对磷酸盐稳态的调节作用主要来源于人类遗传疾病和基因工程小鼠，本文对此进行综述。
In contrast to the regulation of calcium homeostasis, which has been extensively studied over the past several decades, relatively little is known about the regulation of phosphate homeostasis. Fibroblast growth factor 23 (FGF23) is part of a previously unrecognized hormonal bone-parathyroid-kidney axis, which is modulated by PTH, 1,25(OH)2-vitamin D (1,25(OH)2D), dietary and serum phosphorus levels. Synthesis and secretion of FGF23 by osteocytes are positively regulated by 1,25(OH)2D and serum phosphorus and negatively regulated, through yet unknown mechanisms, by the phosphate-regulating gene with homologies to endopeptidases on the X chromosome (PHEX) and by dentin matrix protein 1 (DMP1). In turn, FGF23 inhibits the synthesis of 1,25(OH)2D, and it may negatively regulate the secretion of parathyroid hormone (PTH) from the parathyroid glands. However, FGF23 synergizes with PTH to increase renal phosphate excretion by reducing expression of the renal sodium-phosphate cotransporters NaPi-IIa and NaPi-IIc in the proximal tubules. Most insights gained into the regulation of phosphate homeostasis by these factors are derived from human genetic disorders and genetically engineered mice, which are reviewed in this paper.