Prié Dominique, Beck Laurent, Silve Caroline, Friedlander Gérard
Department of Physiology and Inserm U 426, Faculté de Médecine Xavier Bichat, Université Denis Diderot, Paris, France.
Nephron Exp Nephrol. 2004;98(2):e50-4. doi: 10.1159/000080256.
Our knowledge of phosphate balance under physiological and pathological situations has increased substantially during the last decade thanks to the molecular identification of three dissimilar families of sodium-phosphate cotransport systems, two of them almost exclusively expressed in epithelia whereas the third one has a ubiquitous expression. Intracellular proteins such as NHERF1 (sodium-proton exchanger regulatory factor 1) can interact with phosphate transporters through PDZ domains thus regulating the expression of the transporters at the membrane. Moreover, newly acknowledged paracrine/endocrine peptides, such as fibroblast growth factor 23 (FGF23), also affect the activity of phosphate transporters. Renal phosphate leak, related to invalidation (in the mouse) or to mutations (in humans) of the renal phosphate transporter NPT2a, leads to hypophosphatemia on the one hand, and to nephrolithiasis or bone demineralization on the other hand. Similar features are observed during invalidation of NHERF or in case of overproduction of FGF23. These observations highlight the importance of phosphate homeostasis in common diseases such as renal stones or bone loss.
在过去十年间，得益于对三种不同的钠磷共转运系统家族的分子鉴定，我们对生理和病理情况下磷平衡的认识有了显著提高。其中两个家族几乎仅在上皮细胞中表达，而第三个家族则广泛表达。细胞内蛋白如NHERF1（钠-质子交换调节因子1）可通过PDZ结构域与磷转运体相互作用，从而调节转运体在细胞膜上的表达。此外，新发现的旁分泌/内分泌肽，如成纤维细胞生长因子23（FGF23），也会影响磷转运体的活性。肾磷泄漏与肾磷转运体NPT2a的失活（在小鼠中）或突变（在人类中）有关，一方面会导致低磷血症，另一方面会导致肾结石或骨质脱矿。在NHERF失活或FGF23过度产生的情况下也会观察到类似特征。这些观察结果凸显了磷稳态在肾结石或骨质流失等常见疾病中的重要性。
