INSERM, UMR 1229, RMeS, Regenerative Medicine and Skeleton, Université de Nantes, ONIRIS, Nantes, France.
Université de Nantes, UFR Odontologie, Nantes, France.
J Mol Endocrinol. 2020 Oct;65(3):R53-R63. doi: 10.1530/JME-20-0121.
The critical role of phosphate (Pi) in countless biological processes requires the ability to control its concentration both intracellularly and extracellularly. At the body level, this concentration is finely regulated by numerous hormones, primarily parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23). While this control of the body's Pi homeostasis is now well documented, knowledge of the mechanisms that allow the cell and the body to detect extracellular Pi variations is much less known. These systems are well described in bacteria, yeasts and plants, but as will be discussed in this review, knowledge obtained from these organisms is not entirely relevant to the requirements of Pi biology in mammals. In this review, we present the latest findings on extracellular Pi sensing in mammals, and describe the mammalian Pi sensors identified to date, such as SLC20A1 (PIT1)/SLC20A2 (PIT2) heterodimers and the calcium-sensing receptor (CaSR). While there are many questions remaining to be resolved, a clarification of the Pi sensing mechanisms in mammals is critical to understanding the deregulation of Pi balance in certain life-threatening disease states, such as end-stage renal disease and associated vascular calcifications, and to proposing relevant therapeutic approaches.
磷酸盐（Pi）在无数生物过程中起着关键作用，这就要求其在细胞内和细胞外都能得到有效控制。在机体水平上，Pi 的浓度由许多激素精细调节，主要是甲状旁腺激素（PTH）和成纤维细胞生长因子 23（FGF23）。尽管目前已经很好地记录了机体对 Pi 动态平衡的控制，但对于细胞和机体检测细胞外 Pi 变化的机制的了解则要少得多。这些系统在细菌、酵母和植物中得到了很好的描述，但正如本文综述中所讨论的，从这些生物体中获得的知识并不完全适用于哺乳动物 Pi 生物学的要求。在这篇综述中，我们介绍了哺乳动物细胞外 Pi 感应的最新发现，并描述了迄今为止发现的哺乳动物 Pi 感应器，如 SLC20A1（PIT1）/SLC20A2（PIT2）异二聚体和钙敏感受体（CaSR）。尽管仍有许多问题有待解决，但阐明哺乳动物 Pi 感应机制对于理解某些危及生命的疾病状态下 Pi 平衡的失调至关重要，例如终末期肾病和相关的血管钙化，并提出相关的治疗方法。
