Department of Pediatrics, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390-9063, USA.
Pediatr Nephrol. 2010 Apr;25(4):591-601. doi: 10.1007/s00467-009-1273-z. Epub 2009 Aug 11.
There are a number of hypophosphatemic disorders due to renal phosphate wasting that cannot be explained by elevated levels of parathyroid hormone. The circulating factors responsible for the phosphaturia have been designated as phosphatonins. Studies of patients with tumor-induced osteomalacia and other genetic diseases of phosphate metabolism have resulted in the identification of a number of hormones that regulate phosphate homeostasis, including matrix extracellular phosphoglycoprotein (MEPE), secreted frizzled-related protein 4 (sFRP-4), dentin matrix protein 1 (DMP1), fibroblast growth factor 7 (FGF7), fibroblast growth factor 23 (FGF23), and Klotho. Our understanding of the actions of these hypophosphatemic peptides has been enhanced by studies in mice either overexpressing or not expressing these hormones. This review focuses on FGF23 since its regulation is disordered in diseases that affect children, such as X-linked hypophosphatemia, autosomal dominant and recessive hypophosphatemic rickets as well as chronic kidney disease. Recent studies have shown that FGF23 is unique among the FGFs in its requirement for Klotho for receptor activation. Here, we also discuss new potentially clinically important data pointing to the receptor(s) that mediate the binding and action of FGF23 and Klotho.
存在许多由于肾脏磷酸盐丢失导致的低磷酸盐血症，这些病症不能用甲状旁腺激素水平升高来解释。导致磷酸盐尿的循环因子被指定为磷酸盐转运蛋白。对肿瘤诱导性骨软化症和其他磷酸盐代谢遗传疾病患者的研究导致了许多调节磷酸盐稳态的激素的鉴定，包括基质细胞外磷糖蛋白（MEPE）、分泌卷曲相关蛋白 4（sFRP-4）、牙本质基质蛋白 1（DMP1）、成纤维细胞生长因子 7（FGF7）、成纤维细胞生长因子 23（FGF23）和 Klotho。通过在过度表达或不表达这些激素的小鼠中的研究，我们对这些低磷酸盐肽的作用的理解得到了增强。本篇综述主要关注 FGF23，因为它在影响儿童的疾病中的调节是紊乱的，如 X 连锁低磷酸盐血症、常染色体显性和隐性低磷酸盐性佝偻病以及慢性肾脏病。最近的研究表明，FGF23 在其受体激活需要 Klotho 方面是 FGFs 中的独特存在。在这里，我们还讨论了新的、可能具有临床重要意义的数据，这些数据指出了介导 FGF23 和 Klotho 结合和作用的受体。
