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首页> 外文期刊>Reviews in Endocrine & Metabolic Disorders >The role of vitamin D in the FGF23, klotho, and phosphate bone-kidney endocrine axis
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The role of vitamin D in the FGF23, klotho, and phosphate bone-kidney endocrine axis

机译：维生素D在FGF23，klotho和磷酸盐骨肾内分泌轴中的作用

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摘要

1,25-dihydroxyvitamin D (1,25D), through association with the nuclear vitamin D receptor (VDR), exerts control over a novel endocrine axis consisting of the bone-derived hormone FGF23, and the kidney-expressed klotho, CYP27B1, and CYP24A1 genes, which together prevent hyperphosphatemia/ectopic calcification and govern the levels of 1,25D to maintain bone mineral integrity while promoting optimal function of other vital tissues. When occupied by 1,25D, VDR interacts with RXR to form a heterodimer that binds to VDREs in the region of genes directly controlled by 1,25D (e.g., FGF23, klotho, Npt2c, CYP27B1 and CYP24A1). By recruiting complexes of comodulators, activated VDR initiates a series of events that induces or represses the transcription of genes encoding proteins such as: the osteocyte-derived hormone, FGF23; the renal anti-senescence factor and protein co-receptor for FGF23, klotho; other mediators of phosphate transport including Npt2a/c; and vitamin D hormone metabolic enzymes, CYP27B1 and CYP24A1. The mechanism whereby osteocytes are triggered to release FGF23 is yet to be fully defined, but 1,25D, phosphate, and leptin appear to play major roles. The kidney responds to FGF23 to elicit CYP24A1-catalyzed detoxification of the 1,25D hormone while also repressing both Npt2a/c to mediate phosphate elimination and CYP27B1 to limit de novo 1,25D synthesis. Comprehension of these skeletal and renal actions of 1,25D should facilitate the development of novel mimetics to prevent ectopic calcification, chronic renal and vascular disease, and promote healthful aging.
机译：1,25-二羟基维生素D（1,25D）通过与核维生素D受体（VDR）结合，控制由骨衍生激素FGF23和肾脏表达的克洛索（CYP27B1）组成的新型内分泌轴CYP24A1基因共同防止高磷血症/异位钙化并控制1,25D的水平，以维持骨骼矿物质的完整性，同时促进其他重要组织的最佳功能。当被1,25D占据时，VDR与RXR相互作用形成异二聚体，该异二聚体与直接受1,25D控制的基因区域（例如FGF23，klotho，Npt2c，CYP27B1和CYP24A1）中的VDRE结合。通过募集协同调节剂的复合物，激活的VDR引发了一系列事件，这些事件诱导或抑制编码蛋白质的基因的转录，这些蛋白质例如：骨细胞衍生激素FGF23； FGF23，klotho的肾脏抗衰老因子和蛋白共受体；磷酸盐转运的其他介质，包括Npt2a / c；和维生素D激素代谢酶CYP27B1和CYP24A1。骨细胞触发释放FGF23的机制尚未完全确定，但是1,25D，磷酸盐和瘦蛋白似乎起主要作用。肾脏对FGF23有反应，以引起CYP24A1催化的1,25D激素解毒，同时也抑制Npt2a / c介导磷酸盐消除和CYP27B1抑制从头合成1,25D。理解1,25D的这些骨骼和肾脏作用应有助于开发新型模拟物，以防止异位钙化，慢性肾脏和血管疾病并促进健康的衰老。

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