Titre
Renal Fanconi Syndrome and Hypophosphatemic Rickets in the Absence of Xenotropic and Polytropic Retroviral Receptor in the Nephron.
Type
article
Institution
UNIL/CHUV/Unisanté + institutions partenaires
Périodique
Auteur(s)
Ansermet, C.
Co-première auteure/Co-premier auteur
Moor, M.B.
Co-première auteure/Co-premier auteur
Centeno, G.
Co-première auteure/Co-premier auteur
Auberson, M.
Co-première auteure/Co-premier auteur
Hu, D.Z.
Auteure/Auteur
Baron, R.
Auteure/Auteur
Nikolaeva, S.
Auteure/Auteur
Haenzi, B.
Auteure/Auteur
Katanaeva, N.
Auteure/Auteur
Gautschi, I.
Auteure/Auteur
Katanaev, V.
Auteure/Auteur
Rotman, S.
Auteure/Auteur
Koesters, R.
Auteure/Auteur
Schild, L.
Auteure/Auteur
Pradervand, S.
Auteure/Auteur
Bonny, O.
Co-dernière auteure/Co-dernier auteur
Firsov, D.
Co-dernière auteure/Co-dernier auteur
ISSN
1533-3450
Statut éditorial
Publié
Date de publication
2017-04
Volume
28
Numéro
4
Première page
1073
Dernière page/numéro d’article
1078
Peer-reviewed
Oui
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: ppublish
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.
PID Serval
serval:BIB_2E74785F4FE1
PMID
Date de création
2017-01-06T08:06:28.781Z
Date de création dans IRIS
2025-05-20T18:51:43Z
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Nom
27799484_postprint.pdf
Version du manuscrit
postprint
Taille
8.68 MB
Format
Adobe PDF
PID Serval
serval:BIB_2E74785F4FE1.P001
URN
urn:nbn:ch:serval-BIB_2E74785F4FE12
Somme de contrôle
(MD5):27c18c2ecf7476d609c48e367b65064c