Renal Fanconi Syndrome and Hypophosphatemic Rickets in the Absence of Xenotropic and Polytropic Retroviral Receptor in the Nephron.

Détails

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Etat: Public
Version: Author's accepted manuscript
Licence: Non spécifiée
ID Serval
serval:BIB_2E74785F4FE1
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Renal Fanconi Syndrome and Hypophosphatemic Rickets in the Absence of Xenotropic and Polytropic Retroviral Receptor in the Nephron.
Périodique
Journal of the American Society of Nephrology : JASN
Auteur(s)
Ansermet C. (co-premier), Moor M.B. (co-premier), Centeno G. (co-premier), Auberson M. (co-premier), Hu D.Z., Baron R., Nikolaeva S., Haenzi B., Katanaeva N., Gautschi I., Katanaev V., Rotman S., Koesters R., Schild L., Pradervand S., Bonny O. (co-dernier), Firsov D. (co-dernier)
ISSN
1533-3450 (Electronic)
ISSN-L
1046-6673
Statut éditorial
Publié
Date de publication
04/2017
Peer-reviewed
Oui
Volume
28
Numéro
4
Pages
1073-1078
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: ppublish
Résumé
Tight control of extracellular and intracellular inorganic phosphate (Pi) levels is critical to most biochemical and physiologic processes. Urinary Pi is freely filtered at the kidney glomerulus and is reabsorbed in the renal tubule by the action of the apical sodium-dependent phosphate transporters, NaPi-IIa/NaPi-IIc/Pit2. However, the molecular identity of the protein(s) participating in the basolateral Pi efflux remains unknown. Evidence has suggested that xenotropic and polytropic retroviral receptor 1 (XPR1) might be involved in this process. Here, we show that conditional inactivation of Xpr1 in the renal tubule in mice resulted in impaired renal Pi reabsorption. Analysis of Pi transport in primary cultures of proximal tubular cells or in freshly isolated renal tubules revealed that this Xpr1 deficiency significantly affected Pi efflux. Further, mice with conditional inactivation of Xpr1 in the renal tubule exhibited generalized proximal tubular dysfunction indicative of Fanconi syndrome, characterized by glycosuria, aminoaciduria, calciuria, and albuminuria. Dramatic alterations in the renal transcriptome, including a significant reduction in NaPi-IIa/NaPi-IIc expression, accompanied these functional changes. Additionally, Xpr1-deficient mice developed hypophosphatemic rickets secondary to renal dysfunction. These results identify XPR1 as a major regulator of Pi homeostasis and as a potential therapeutic target in bone and kidney disorders.
Pubmed
Web of science
Financement(s)
Fonds national suisse / Projets / 31003A-149440
Fonds national suisse / Projets / 310030-163340
Création de la notice
06/01/2017 9:06
Dernière modification de la notice
24/01/2020 6:19
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