Department of Neuroscience, Physiology and Pharmacology, Royal Free Campus, University College London, London NW3 2PF, UK.
CHU de Nantes, Université de Nantes, F-44042 Nantes, France.
Int J Mol Sci. 2021 May 27;22(11):5701. doi: 10.3390/ijms22115701.
Phosphate homeostasis is essential for health and is achieved via interaction between the bone, kidney, small intestine, and parathyroid glands and via intricate processes involving phosphate transporters, phosphate sensors, and circulating hormones. Numerous genetic and acquired disorders are associated with disruption in these processes and can lead to significant morbidity and mortality. The role of the kidney in phosphate homeostasis is well known, although it is recognized that the cellular mechanisms in murine models and humans are different. Intestinal phosphate transport also appears to differ in humans and rodents, with recent studies demonstrating a dominant role for the paracellular pathway. The existence of phosphate sensing has been acknowledged for decades; however, the underlying molecular mechanisms are poorly understood. At least three phosphate sensors have emerged. PiT2 and FGFR1c both act as phosphate sensors controlling Fibroblast Growth Factor 23 secretion in bone, whereas the calcium-sensing receptor controls parathyroid hormone secretion in response to extracellular phosphate. All three of the proposed sensors are expressed in the kidney and intestine but their exact function in these organs is unknown. Understanding organ interactions and the mechanisms involved in phosphate sensing requires significant research to develop novel approaches for the treatment of phosphate homeostasis disorders.
磷酸盐稳态对于健康至关重要，它是通过骨骼、肾脏、小肠和甲状旁腺之间的相互作用以及涉及磷酸盐转运蛋白、磷酸盐传感器和循环激素的复杂过程来实现的。许多遗传和获得性疾病与这些过程的紊乱有关，并可能导致严重的发病率和死亡率。肾脏在磷酸盐稳态中的作用是众所周知的，尽管人们认识到鼠模型和人类中的细胞机制是不同的。肠道磷酸盐转运似乎在人类和啮齿动物中也存在差异，最近的研究表明，细胞旁途径起着主导作用。几十年来，人们已经认识到磷酸盐感应的存在；然而，其潜在的分子机制还了解甚少。至少有三种磷酸盐传感器已经出现。PiT2 和 FGFR1c 都作为磷酸盐传感器起作用，控制骨骼中成纤维细胞生长因子 23 的分泌，而钙敏感受体则控制甲状旁腺激素的分泌，以响应细胞外磷酸盐。这三个拟议的传感器都在肾脏和肠道中表达，但它们在这些器官中的确切功能尚不清楚。了解器官相互作用和磷酸盐感应涉及的机制需要进行大量研究，以开发治疗磷酸盐稳态紊乱的新方法。
