Glut9 is a major regulator of urate homeostasis and its genetic inactivation induces hyperuricosuria and urate nephropathy.

Détails

ID Serval
serval:BIB_1EC881C9D168
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Glut9 is a major regulator of urate homeostasis and its genetic inactivation induces hyperuricosuria and urate nephropathy.
Périodique
Proceedings of the National Academy of Sciences of the United States of America
Auteur(s)
Preitner F., Bonny O., Laverrière A., Rotman S., Firsov D., Da Costa A., Metref S., Thorens B.
ISSN
1091-6490[electronic]
Statut éditorial
Publié
Date de publication
2009
Volume
106
Numéro
36
Pages
15501-15506
Langue
anglais
Résumé
Elevated plasma urate levels are associated with metabolic, cardiovascular, and renal diseases. Urate may also form crystals, which can be deposited in joints causing gout and in kidney tubules inducing nephrolithiasis. In mice, plasma urate levels are controlled by hepatic breakdown, as well as, by incompletely understood renal processes of reabsorption and secretion. Here, we investigated the role of the recently identified urate transporter, Glut9, in the physiological control of urate homeostasis using mice with systemic or liver-specific inactivation of the Glut9 gene. We show that Glut9 is expressed in the basolateral membrane of hepatocytes and in both apical and basolateral membranes of the distal nephron. Mice with systemic knockout of Glut9 display moderate hyperuricemia, massive hyperuricosuria, and an early-onset nephropathy, characterized by obstructive lithiasis, tubulointerstitial inflammation, and progressive inflammatory fibrosis of the cortex, as well as, mild renal insufficiency. In contrast, liver-specific inactivation of the Glut9 gene in adult mice leads to severe hyperuricemia and hyperuricosuria, in the absence of urate nephropathy or any structural abnormality of the kidney. Together, our data show that Glut9 plays a major role in urate homeostasis by its dual role in urate handling in the kidney and uptake in the liver.
Pubmed
Web of science
Open Access
Oui
Création de la notice
07/10/2009 15:47
Dernière modification de la notice
20/08/2019 12:54
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