[alpha Klotho and inorganic phosphate metabolism].
Recent studies have demonstrated that klotho protein plays a role in calcium/phosphate homeostasis. Urakawa et al demonstrated that the concerted action of klotho and fibroblast growth factor receptor 1 reconstitutes the fibroblast growth factor 23 (FGF23) receptor (Nature 444,770,2006). We investigated the correlation between hyperphosphatemia and Pi transport activity in klotho mutant mice (kl/kl mice). kl/kl mice displayed hyperphosphatemia, high plasma 1,25 (OH) (2)D(3) levels, increased activity of the renal and intestinal sodium-dependent P (i) cotransporters, and increased levels of the type II a, type II b, and type II c transporter proteins compared with wild-type mice. Interestingly, transcript levels of the type II a/type II c transporter mRNA abundance, but not transcripts levels of type II b transporter mRNA, were markedly decreased in kl/kl mice compared with wild-type mice. Furthermore, plasma FGF23 levels were 150-fold higher in kl/kl mice than in wild-type mice. Feeding of a low-P (i) 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. These results indicate that hyperphosphatemia in klotho mice is due to dysregulation of expression and trafficking of the renal type II a/ II c transporters rather than to intestinal P (i) uptake.
Miyamoto
Ken-ichi
K
The University of Tokushima Graduate School, Institution of Health Biosciences, Department of Molecular Nutrition, Japan.
Segawa
Hiroko
H
Ito
Mikiko
M
Tatsumi
Sawako
S
D000818:Animals; D004705:Endocytosis / Q000502:physiology; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000378:metabolism; D005966:Glucuronidase / Q000502:physiology*; D006023:Glycoproteins / Q000378:metabolism; D000090265:Klotho Proteins; D051379:Mice; D008817:Mice, Mutant Strains; D053402:PHEX Phosphate Regulating Neutral Endopeptidase / Q000378:metabolism; D010710:Phosphates / Q000097:blood / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism
D016326:Extracellular Matrix Proteins; C000717428:Fgf23 protein, mouse; D006023:Glycoproteins; C518716:Mepe protein, mouse; D010710:Phosphates; D010750:Phosphoproteins; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; D005966:Glucuronidase; D000090265:Klotho Proteins; D053402:PHEX Phosphate Regulating Neutral Endopeptidase; C506232:Phex protein, mouse