The FGF23-Klotho axis: endocrine regulation of phosphate homeostasis.
The FGF23-Klotho axis: endocrine regulation of phosphate homeostasis.
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DOI：
10.1038/nrendo.2009.196
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发表时间：
2009-11
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体内适当的磷酸盐水平是通过骨源性生长因子FGF23和膜结合蛋白Klotho的协调调节维持的。FGF23的内分泌作用，与甲状旁腺激素和维生素D相关，动员磷酸钠共转运体，控制近端小管上皮细胞中肾磷酸盐的运输。足量的Klotho对于FGF23在肾脏中发挥其磷酸化作用至关重要。在Klotho存在的情况下，FGF23激活影响磷酸盐稳态的下游信号成分，而在没有这种膜蛋白的情况下，它无法发挥这种调节作用，这在动物模型中得到了令人信服的证明。包括磷酸盐和维生素D在内的几个因素可以调节FGF23和Klotho的产生并影响它们的功能。在各种获得性和遗传性人类疾病中，由于磷酸盐转换改变，FGF23和Klotho的失调与血管和骨骼异常有关。在这篇综述中，我总结了骨源性FGF23如何协同Klotho调节全身磷酸盐稳态的内分泌作用，以及这些分子平衡不足如何导致矿物质离子代谢异常引起的并发症。
Appropriate levels of phosphate in the body are maintained by the coordinated regulation of the bone-derived growth factor FGF23 and the membrane-bound protein Klotho. The endocrine actions of FGF23, in association with parathyroid hormone and vitamin D, mobilize sodium–phosphate cotransporters that control renal phosphate transport in proximal tubular epithelial cells. The availability of an adequate amount of Klotho is essential for FGF23 to exert its phosphaturic effects in the kidney. In the presence of Klotho, FGF23 activates downstream signaling components that influence the homeostasis of phosphate, whereas in the absence of this membrane protein, it is unable to exert such regulatory effects, as demonstrated convincingly in animal models. Several factors, including phosphate and vitamin D, can regulate the production of both FGF23 and Klotho and influence their functions. In various acquired and genetic human diseases, dysregulation of FGF23 and Klotho is associated with vascular and skeletal anomalies owing to altered phosphate turnover. In this Review, I summarize how the endocrine effects of bone-derived FGF23, in coordination with Klotho, can regulate systemic phosphate homeostasis, and how an inadequate balance of these molecules can lead to complications that are caused by abnormal mineral ion metabolism.