FGF23 的生理学和与肾脏磷丢失相关的遗传疾病概述。

Physiology of FGF23 and overview of genetic diseases associated with renal phosphate wasting.

机构信息

Reference Center for Rare Renal Disorders, Reference Center for Rare Disorders of Calcium and Phosphate Metabolism, Department of Pediatric Nephrology, Rheumatology and Dermatology, Femme Mère Enfant Hospital, Bron Cedex, France; Lyon-Est Medical School, Lyon 1 University, Lyon, France; INSERM 1033, LYOS, Bone Disorders Prevention, Lyon, France.

Paris Descartes University, EA2496, Faculty of Dental Surgery, Montrouge, France.

出版信息

Metabolism. 2020 Feb;103S:153865. doi: 10.1016/j.metabol.2019.01.006. Epub 2019 Jan 19.

DOI:10.1016/j.metabol.2019.01.006

PMID:30664852

Abstract

Phosphate is a cornerstone of several physiological pathways including skeletal development, bone mineralization, membrane composition, nucleotide structure, maintenance of plasma pH, and cellular signaling. The kidneys have a key role in phosphate homeostasis with three hormones having important functions in renal phosphate handling or intestinal absorption: parathyroid hormone (PTH), fibroblast growth factor 23 (FGF23), and 1-25-dihydroxyvitamin D (1,25(OH)2D). FGF23 is mainly synthesized by osteocytes; it is a direct phosphaturic factor that also inhibits 1,25(OH)2D and PTH. In addition to crucial effects on phosphate and calcium metabolism, FGF23 also has 'off-target' effects notably on the cardiovascular, immune and central nervous systems. Genetic diseases may affect the FGF23 pathway, resulting in either increased FGF23 levels leading to hypophosphatemia (such as in X-linked hypophosphatemia) or defective secretion/action of intact FGF23 inducing hyperphosphatemia (such as in familial tumoral calcinosis). The aim of this review is to provide an overview of FGF23 physiology and pathophysiology in X-linked hypophosphatemia, with a focus on FGF23-associated genetic diseases.

摘要

磷酸盐是包括骨骼发育、骨矿化、膜组成、核苷酸结构、维持血浆 pH 值和细胞信号在内的几种生理途径的基石。肾脏在磷酸盐稳态中起着关键作用，三种激素在肾脏磷酸盐处理或肠道吸收中具有重要功能：甲状旁腺激素 (PTH)、成纤维细胞生长因子 23 (FGF23) 和 1-25-二羟维生素 D (1,25(OH)2D)。FGF23 主要由骨细胞合成；它是一种直接的排磷酸盐因子，还抑制 1,25(OH)2D 和 PTH。除了对磷酸盐和钙代谢有重要影响外，FGF23 还对心血管、免疫和中枢神经系统有“非靶向”作用。遗传疾病可能会影响 FGF23 途径，导致 FGF23 水平升高导致低磷酸盐血症（如 X 连锁低磷酸盐血症），或完整 FGF23 的分泌/作用缺陷导致高磷酸盐血症（如家族性肿瘤性钙质沉着症）。本综述的目的是概述 X 连锁低磷酸盐血症中 FGF23 的生理学和病理生理学，重点介绍与 FGF23 相关的遗传疾病。