Hypophosphatemia and calcium nephrolithiasis.
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.
Prié
Dominique
D
Department of Physiology and Inserm U 426, Faculté de Médecine Xavier Bichat, Université Denis Diderot, Paris, France.
Beck
Laurent
L
Silve
Caroline
C
Friedlander
Gérard
G
D000818:Animals; D001862:Bone Resorption; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000502:physiology; D006706:Homeostasis; D006801:Humans; D017674:Hypophosphatemia / Q000209:etiology* / Q000503:physiopathology*; D007669:Kidney Calculi / Q000235:genetics* / Q000503:physiopathology*; D051379:Mice; D028061:Phosphate Transport Proteins / Q000502:physiology; D010710:Phosphates / Q000378:metabolism*; D010750:Phosphoproteins / Q000235:genetics / Q000502:physiology; D017923:Sodium-Hydrogen Exchangers
C000717427:FGF23 protein, human; C000717428:Fgf23 protein, mouse; D028061:Phosphate Transport Proteins; D010710:Phosphates; D010750:Phosphoproteins; D017923:Sodium-Hydrogen Exchangers; C093376:sodium-hydrogen exchanger regulatory factor; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23