The rapid rise in circulating fibroblast growth factor 23 (FGF23) associated with kidney injury results in calcitriol deficiency, altered calcium homeostasis, and secondary hyperparathyroidism, and may contribute to cardiovascular complications and death. However, the mechanisms of increased FGF23 in states of kidney injury remain unclear. In this issue of the JCI, Simic et al. screened plasma taken from the renal vein of patients undergoing cardiac catheterization and identified glycerol-3-phosphate (G-3-P) as the most significant correlate of simultaneous arterial FGF23 levels. When G-3-P was administered to mice, FGF23 production increased in bone. In a series of elegant mouse studies, the authors discovered a pathway linking increased G-3-P to increased FGF23 via increases in lysophosphatidic acid (LPA), which activates the LPA receptor 1 in FGF23-secreting cells in the bone and bone marrow. Although the authors present human data that broadly support the results from the mouse models, further research is needed to determine whether targeting the G-3-P/FGF23 pathway has the potential to modify FGF23-related complications in the clinic.

中文翻译：

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肾脏通过床头到长凳……再回到骨头？

与肾脏损伤相关的循环成纤维细胞生长因子23（FGF23）的快速升高导致钙三醇缺乏，钙稳态改变和继发性甲状旁腺功能亢进，并可能导致心血管并发症和死亡。然而，在肾损伤状态下增加FGF23的机制仍不清楚。在JCI的这一期中，Simic等人。筛选了从接受心脏导管插入术的患者的肾静脉中取出的血浆，并将甘油3-磷酸（G-3-P）鉴定为同时动脉FGF23水平的最显着相关因素。当对小鼠施用G-3-P时，骨骼中FGF23的产量增加。在一系列出色的小鼠研究中，作者发现了一条途径，即通过溶血磷脂酸（LPA）的增加将增加的G-3-P与增加的FGF23连接起来，它激活骨骼和骨髓中FGF23分泌细胞中的LPA受体1。尽管作者提供的人类数据广泛支持小鼠模型的结果，但仍需要进一步研究以确定靶向G-3-P / FGF23途径是否具有在临床中修饰FGF23相关并发症的潜力。