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

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Serval ID
serval:BIB_2E74785F4FE1
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Renal Fanconi Syndrome and Hypophosphatemic Rickets in the Absence of Xenotropic and Polytropic Retroviral Receptor in the Nephron.
Journal
Journal of the American Society of Nephrology : JASN
Author(s)
Ansermet C. (co-first), Moor M.B. (co-first), Centeno G. (co-first), Auberson M. (co-first), 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-last), Firsov D. (co-last)
ISSN
1533-3450 (Electronic)
ISSN-L
1046-6673
Publication state
Published
Issued date
04/2017
Peer-reviewed
Oui
Volume
28
Number
4
Pages
1073-1078
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Abstract
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
Funding(s)
Swiss National Science Foundation / Projects / 31003A-149440
Swiss National Science Foundation / Projects / 310030-163340
Create date
06/01/2017 9:06
Last modification date
17/09/2020 8:24
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