Colosaal Biosciences, Dallas, TX, USA.
Division of Pediatric Nephrology, Department of Pediatrics, The University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX, USA.
Pediatr Nephrol. 2024 Dec;39(12):3439-3451. doi: 10.1007/s00467-024-06395-5. Epub 2024 Jun 14.
Phosphate is essential for numerous biological processes, and serum levels are tightly regulated to accomplish these functions. The regulation of serum phosphate in a narrow physiological range is a well-orchestrated process and involves the gastrointestinal (GI) tract, bone, kidneys, and several hormones, namely, parathyroid hormone, fibroblast growth factor 23 (FGF23), and 1,25-dihydroxyvitamin D (1,25 Vitamin D). Although primarily synthesized in the bone, FGF23, an endocrine FGF, acts on the kidney to regulate phosphate and Vitamin D homeostasis by causing phosphaturia and reduced levels of 1,25 Vitamin D. Recent studies have highlighted the complex regulation of FGF23 including transcriptional and post-translational modification and kidney-bone cross talk. Understanding FGF23 biology has led to the identification of novel therapeutic agents to treat diseases that disrupt phosphate metabolism secondary to FGF23. The focus of this review is to provide an overview of phosphate homeostasis, FGF23 biology, and the role of FGF23 in phosphate balance.
磷酸盐对许多生物过程至关重要，其血清水平受到严格调节以完成这些功能。血清磷酸盐在狭窄的生理范围内的调节是一个协调良好的过程，涉及胃肠道 (GI) 道、骨骼、肾脏和几种激素，即甲状旁腺激素、成纤维细胞生长因子 23 (FGF23) 和 1,25-二羟维生素 D (1,25 Vitamin D)。尽管 FGF23 主要在骨骼中合成，但它是一种内分泌 FGF，通过引起磷酸尿和 1,25 Vitamin D 水平降低，在肾脏中发挥作用，调节磷酸盐和维生素 D 稳态。最近的研究强调了 FGF23 的复杂调节，包括转录和翻译后修饰以及肾脏-骨骼的相互作用。对 FGF23 生物学的理解导致了新型治疗剂的鉴定，以治疗因 FGF23 而破坏磷酸盐代谢的疾病。本综述的重点是概述磷酸盐稳态、FGF23 生物学以及 FGF23 在磷酸盐平衡中的作用。
