Renal Ca2+ wasting, hyperabsorption, and reduced bone thickness in mice lacking TRPV5

Détails

ID Serval
serval:BIB_E7CD2AE6B54D
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Renal Ca2+ wasting, hyperabsorption, and reduced bone thickness in mice lacking TRPV5
Périodique
Journal of Clinical Investigation
Auteur(s)
Hoenderop J. G., van Leeuwen J. P., van der Eerden B. C., Kersten F. F., van der Kemp A. W., Mérillat A. M., Waarsing J. H., Rossier B. C., Vallon V., Hummler E., Bindels R. J.
ISSN
0021-9738
Statut éditorial
Publié
Date de publication
12/2003
Peer-reviewed
Oui
Volume
112
Numéro
12
Pages
1906-14
Notes
Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. --- Old month value: Dec
Résumé
Ca2+ ions play a fundamental role in many cellular processes, and the extracellular concentration of Ca2+ is kept under strict control to allow the proper physiological functions to take place. The kidney, small intestine, and bone determine the Ca2+ flux to the extracellular Ca2+ pool in a concerted fashion. Transient receptor potential (TRP) cation channel subfamily V, members 5 and 6 (TRPV5 and TRPV6) have recently been postulated to be the molecular gatekeepers facilitating Ca2+ influx in these tissues and are members of the TRP family, which mediates diverse biological effects ranging from pain perception to male aggression. Genetic ablation of TRPV5 in the mouse allowed us to investigate the function of this novel Ca2+ channel in maintaining the Ca2+ balance. Here, we demonstrate that mice lacking TRPV5 display diminished active Ca2+ reabsorption despite enhanced vitamin D levels, causing severe hypercalciuria. In vivo micropuncture experiments demonstrated that Ca2+ reabsorption was malfunctioning within the early part of the distal convolution, exactly where TRPV5 is localized. In addition, compensatory hyperabsorption of dietary Ca2+ was measured in TRPV5 knockout mice. Furthermore, the knockout mice exhibited significant disturbances in bone structure, including reduced trabecular and cortical bone thickness. These data demonstrate the key function of TRPV5 in active Ca2+ reabsorption and its essential role in the Ca2+ homeostasis.
Mots-clé
Absorption Animals Bone and Bones/*physiology Calcium/*metabolism Calcium Channels/*genetics/*metabolism/*physiology Calcium Signaling Cations Female Femur/metabolism Gene Library Genotype Immunohistochemistry Ions Kidney/*metabolism Kidney Diseases/metabolism Male Mice Mice, Knockout Models, Genetic Osteoporosis Phenotype Potassium/metabolism Reverse Transcriptase Polymerase Chain Reaction Sodium/metabolism TRPV Cation Channels Time Factors
Pubmed
Web of science
Open Access
Oui
Création de la notice
24/01/2008 14:00
Dernière modification de la notice
20/08/2019 17:10
Données d'usage