Correlation between hyperphosphatemia and type II Na-Pi cotransporter activity in klotho mice
- 1 February 2007
- journal article
- Published by American Physiological Society in American Journal of Physiology-Renal Physiology
- Vol. 292 (2), F769-F779
- https://doi.org/10.1152/ajprenal.00248.2006
Abstract
Recent studies have demonstrated that klotho protein plays a role in calcium/phosphate homeostasis. The goal of the present study was to investigate the regulation of Na-Pi cotransporters in klotho mutant (kl/kl) mice. The kl/kl mice displayed hyperphosphatemia, high plasma 1,25(OH)2D3 levels, increased activity of the renal and intestinal sodium-dependent Pi cotransporters, and increased levels of the type IIa, type IIb, and type IIc transporter proteins compared with wild-type mice. Interestingly, transcript levels of the type IIa/type IIc transporter mRNA abundance, but not transcripts levels of type IIb transporter mRNA, were markedly decreased in kl/kl mice compared with wild-type mice. Furthermore, plasma fibroblast growth factor 23 (FGF23) levels were 150-fold higher in kl/kl mice than in wild-type mice. Feeding of a low-Pi diet induced the expression of klotho protein and decreased plasma FGF23 levels in kl/kl mice, whereas colchicine treatment experiments revealed evidence of abnormal membrane trafficking of the type IIa transporter in kl/kl mice. Finally, feeding of a low-Pi diet resulted in increased type IIa Na-Pi cotransporter protein in the apical membrane in the wild-type mice, but not in kl/kl mice. These results indicate that hyperphosphatemia in klotho mice is due to dysregulation of expression and trafficking of the renal type IIa/IIc transporters rather than to intestinal Pi uptake.Keywords
This publication has 32 references indexed in Scilit:
- Regulation of Fibroblast Growth Factor-23 Signaling by KlothoPublished by Elsevier BV ,2006
- The ß-Glucuronidase Klotho Hydrolyzes and Activates the TRPV5 ChannelScience, 2005
- Role of the vitamin D receptor in FGF23 action on phosphate metabolismBiochemical Journal, 2005
- Transgenic Mice Overexpressing Human Fibroblast Growth Factor 23 (R176Q) Delineate a Putative Role for Parathyroid Hormone in Renal Phosphate Wasting DisordersEndocrinology, 2004
- Transgenic Mice Expressing Fibroblast Growth Factor 23 under the Control of the α1(I) Collagen Promoter Exhibit Growth Retardation, Osteomalacia, and Disturbed Phosphate HomeostasisEndocrinology, 2004
- Physiological Regulation of Renal Sodium-Dependent Phosphate CotransportersThe Japanese Journal of Physiology, 2004
- Regulation of Fibroblastic Growth Factor 23 Expression but Not Degradation by PHEXPublished by Elsevier BV ,2003
- Independent impairment of osteoblast and osteoclast differentiation in klotho mouse exhibiting low-turnover osteopeniaJCI Insight, 1999
- Microtubule-Dependent Vesicle Transport: Modulation of Channel and Transporter Activity in Liver and KidneyPhysiological Reviews, 1998
- Mutation of the mouse klotho gene leads to a syndrome resembling ageingNature, 1997