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Vitamin D and type II sodium-dependent phosphate cotransporters.
Contrib Nephrol 2013; 180:86-97CN

Abstract

The type II sodium-dependent Pi (NaPi) cotransporters (NaPi-IIa, NaPi-IIb and NaPi-IIc) contribute to renal and intestinal Pi absorption. 1,25-Dihydroxyvitamin D [1,25(OH)2D3] is an important factor for NaPi-II transporters in the small intestine and kidney. In a previous study, low levels of 1,25(OH)2D3 appeared to suppress the expression of renal NaPi cotransporters. We identified a functional vitamin D receptor-responsive element in the human NaPi-IIa and NaPi-IIc genes in renal epithelial cells. In an analysis of vitamin D receptor (VDR)-null mice, we observed early onset of hypophosphatemia. The cause of the hypophosphatemia in VDR-null mice before weaning appeared to be increased plasma parathyroid hormone (PTH) levels during the suckling periods. A rescue diet (high calcium diet) decreased plasma PTH levels in VDR-null mice. The reduced plasma PTH levels normalized the renal Npt2a and Npt2c protein levels in weanling animals. Thus, the dietary intervention completely normalized the expression of the renal Pi transporters (Npt2a/Npt2c) in VDR-null mice, suggesting that the lack of VDR activity was not the cause of the impaired renal Pi reabsorption. In suckling animals, 1,25(OH)2D3 may be essential for the prevention of the phosphaturic action of PTH. In adult animals, 1,25(OH)2D3 is thought to be an important factor for posttranscriptional regulation of the Npt2b gene in the small intestine. Fibroblast growth factor 23 (FGF23) is a novel phosphaturic factor that influences vitamin D metabolism and renal reabsorption of Pi. We characterized the role of the VDR in the action of FGF23 using VDR-null mice. FGF23 reduced renal Pi transport and 25-hydroxyvitamin D 1a-hydroxylase levels by a mechanism that was independent of the VDR. By contrast, the induction of 25-hydroxyvitamin D 24-hydroxylase and the reduction in serum 1,25(OH)2D3 levels induced by FGF23 were dependent on the VDR. Thus, the VDR is not essential for the phosphaturic action of FGF23, but is essential for control of the plasma 1,25(OH)2D3 level. Moreover, FGF23 reduces intestinal NaPi transport activity and Npt2b protein levels by a mechanism that is dependent on the VDR. Klotho functions as a co-receptor for FGF23 and is increased by 1,25(OH)2D3. Klotho induces phosphaturia by inhibiting the renal NaPi-IIa transporter. In this review, we discuss the roles of 1,25(OH)2D3/VDR in the regulation of renal type II NaPi cotransporters in the kidney and small intestine.

Authors+Show Affiliations

Department of Molecular Nutrition, University of Tokushima Graduate School, 3-18-15 Kuramoto-cho, Tokushima, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

23652552

Citation

Kido, Shinsuke, et al. "Vitamin D and Type II Sodium-dependent Phosphate Cotransporters." Contributions to Nephrology, vol. 180, 2013, pp. 86-97.
Kido S, Kaneko I, Tatsumi S, et al. Vitamin D and type II sodium-dependent phosphate cotransporters. Contrib Nephrol. 2013;180:86-97.
Kido, S., Kaneko, I., Tatsumi, S., Segawa, H., & Miyamoto, K. (2013). Vitamin D and type II sodium-dependent phosphate cotransporters. Contributions to Nephrology, 180, pp. 86-97. doi:10.1159/000346786.
Kido S, et al. Vitamin D and Type II Sodium-dependent Phosphate Cotransporters. Contrib Nephrol. 2013;180:86-97. PubMed PMID: 23652552.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Vitamin D and type II sodium-dependent phosphate cotransporters. AU - Kido,Shinsuke, AU - Kaneko,Ichiro, AU - Tatsumi,Sawako, AU - Segawa,Hiroko, AU - Miyamoto,Ken-ichi, Y1 - 2013/05/06/ PY - 2013/5/9/entrez PY - 2013/5/9/pubmed PY - 2014/1/22/medline SP - 86 EP - 97 JF - Contributions to nephrology JO - Contrib Nephrol VL - 180 N2 - The type II sodium-dependent Pi (NaPi) cotransporters (NaPi-IIa, NaPi-IIb and NaPi-IIc) contribute to renal and intestinal Pi absorption. 1,25-Dihydroxyvitamin D [1,25(OH)2D3] is an important factor for NaPi-II transporters in the small intestine and kidney. In a previous study, low levels of 1,25(OH)2D3 appeared to suppress the expression of renal NaPi cotransporters. We identified a functional vitamin D receptor-responsive element in the human NaPi-IIa and NaPi-IIc genes in renal epithelial cells. In an analysis of vitamin D receptor (VDR)-null mice, we observed early onset of hypophosphatemia. The cause of the hypophosphatemia in VDR-null mice before weaning appeared to be increased plasma parathyroid hormone (PTH) levels during the suckling periods. A rescue diet (high calcium diet) decreased plasma PTH levels in VDR-null mice. The reduced plasma PTH levels normalized the renal Npt2a and Npt2c protein levels in weanling animals. Thus, the dietary intervention completely normalized the expression of the renal Pi transporters (Npt2a/Npt2c) in VDR-null mice, suggesting that the lack of VDR activity was not the cause of the impaired renal Pi reabsorption. In suckling animals, 1,25(OH)2D3 may be essential for the prevention of the phosphaturic action of PTH. In adult animals, 1,25(OH)2D3 is thought to be an important factor for posttranscriptional regulation of the Npt2b gene in the small intestine. Fibroblast growth factor 23 (FGF23) is a novel phosphaturic factor that influences vitamin D metabolism and renal reabsorption of Pi. We characterized the role of the VDR in the action of FGF23 using VDR-null mice. FGF23 reduced renal Pi transport and 25-hydroxyvitamin D 1a-hydroxylase levels by a mechanism that was independent of the VDR. By contrast, the induction of 25-hydroxyvitamin D 24-hydroxylase and the reduction in serum 1,25(OH)2D3 levels induced by FGF23 were dependent on the VDR. Thus, the VDR is not essential for the phosphaturic action of FGF23, but is essential for control of the plasma 1,25(OH)2D3 level. Moreover, FGF23 reduces intestinal NaPi transport activity and Npt2b protein levels by a mechanism that is dependent on the VDR. Klotho functions as a co-receptor for FGF23 and is increased by 1,25(OH)2D3. Klotho induces phosphaturia by inhibiting the renal NaPi-IIa transporter. In this review, we discuss the roles of 1,25(OH)2D3/VDR in the regulation of renal type II NaPi cotransporters in the kidney and small intestine. SN - 1662-2782 UR - https://www.unboundmedicine.com/medline/citation/23652552/Vitamin_D_and_type_II_sodium_dependent_phosphate_cotransporters_ L2 - https://www.karger.com?DOI=10.1159/000346786 DB - PRIME DP - Unbound Medicine ER -