Intestinal and renal adaptation to a low-Pi diet of type II NaPi cotransporters in vitamin D receptor- and 1alphaOHase-deficient mice.
Intake of a low-phosphate diet stimulates transepithelial transport of Pi in small intestine as well as in renal proximal tubules. In both organs, this is paralleled by a change in the abundance of the apically localized NaPi cotransporters NaPi type IIa (NaPi-IIa) and NaPi type IIb (NaPi-IIb), respectively. Low-Pi diet, via stimulation of the activity of the renal 25-hydroxyvitamin-D3-1alpha-hydroxylase (1alphaOHase), leads to an increase in the level of 1,25-dihydroxy-vitamin D3 [1,25(OH)2D]. Regulation of the intestinal absorption of Pi and the abundance of NaPi-IIb by 1,25(OH)2D has been supposed to involve the vitamin D receptor (VDR). In this study, we investigated the adaptation to a low-Pi diet of NaPi-IIb in small intestine as well as NaPi-IIa in kidneys of either VDR- or 1alphaOHase-deficient mice. In both mouse models, upregulation by a low-Pi diet of the NaPi cotransporters NaPi-IIa and NaPi-IIb was normal, i.e., similar to that observed in the wild types. Also, in small intestines of VDR- and 1alphaOHase-deficient mice, the same changes in NaPi-IIb mRNA found in wild-type mice were observed. On the basis of the results, we conclude that the regulation of NaPi cotransport in small intestine (via NaPi-IIb) and kidney (via NaPi-IIa) by low dietary intake of Pi cannot be explained by the 1,25(OH)2D-VDR axis.
Capuano
Paola
P
Institute of Physiology, University of Zurich, Zurich, Switzerland.
Radanovic
Tamara
T
Wagner
Carsten A
CA
Bacic
Desa
D
Kato
Shigeaki
S
Uchiyama
Yasushi
Y
St-Arnoud
René
R
Murer
Heini
H
Biber
Jürg
J
D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase / Q000172:deficiency*; D000222:Adaptation, Physiological; D000818:Animals; D015153:Blotting, Western; D004591:Electrophoresis, Polyacrylamide Gel; D007422:Intestines / Q000502:physiology*; D007668:Kidney / Q000502:physiology*; D051379:Mice; D009924:Organ Culture Techniques; D016226:Phosphorus, Dietary; D012333:RNA, Messenger / Q000032:analysis; D018167:Receptors, Calcitriol / Q000172:deficiency*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050608:Sodium-Phosphate Cotransporter Proteins; D050610:Sodium-Phosphate Cotransporter Proteins, Type II; D050613:Sodium-Phosphate Cotransporter Proteins, Type IIa; D050614:Sodium-Phosphate Cotransporter Proteins, Type IIb; D027981:Symporters / Q000378:metabolism*
D016226:Phosphorus, Dietary; D012333:RNA, Messenger; D018167:Receptors, Calcitriol; C493555:Slc34a1 protein, mouse; C493558:Slc34a2 protein, mouse; D050608:Sodium-Phosphate Cotransporter Proteins; D050610:Sodium-Phosphate Cotransporter Proteins, Type II; D050613:Sodium-Phosphate Cotransporter Proteins, Type IIa; D050614:Sodium-Phosphate Cotransporter Proteins, Type IIb; D027981:Symporters; D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase