Vitamin D3 suppresses Npt2c abundance and differentially modulates phosphate and calcium homeostasis in Npt2a knockout mice.
Sci Rep
; 14(1): 16997, 2024 07 23.
Article
en En
| MEDLINE
| ID: mdl-39043847
ABSTRACT
Vitamin D3 is clinically used for the treatment of vitamin D3 deficiency or osteoporosis, partially because of its role in regulating phosphate (Pi) and calcium (Ca2+) homeostasis. The renal sodium-phosphate cotransporter 2a (Npt2a) plays an important role in Pi homeostasis; however, the role of vitamin D3 in hypophosphatemia has never been investigated. We administered vehicle or vitamin D3 to wild-type (WT) mice or hypophosphatemic Npt2a-/- mice. In contrast to WT mice, vitamin D3 treatment increased plasma Pi levels in Npt2a-/- mice, despite similar levels of reduced parathyroid hormone and increased fibroblast growth factor 23. Plasma Ca2+ was increased ~ twofold in both genotypes. Whereas WT mice were able to increase urinary Pi and Ca2+/creatinine ratios, in Npt2a-/- mice, Pi/creatinine was unchanged and Ca2+/creatinine drastically decreased, coinciding with the highest kidney Ca2+ content, highest plasma creatinine, and greatest amount of nephrocalcinosis. In Npt2a-/- mice, vitamin D3 treatment completely diminished Npt2c abundance, so that mice resembled Npt2a/c double knockout mice. Abundance of intestinal Npt2b and claudin-3 (tight junctions protein) were reduced in Npt2a-/- only, the latter might facilitate the increase in plasma Pi in Npt2a-/- mice. Npt2a might function as regulator between renal Ca2+ excretion and reabsorption in response to vitamin D3.
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Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Fosfatos
/
Calcio
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Ratones Noqueados
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Colecalciferol
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Proteínas Cotransportadoras de Sodio-Fosfato de Tipo IIa
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Homeostasis
Idioma:
En
Revista:
Sci Rep
/
Sci. rep. (Nat. Publ. Group)
/
Scientific reports (Nature Publishing Group)
Año:
2024
Tipo del documento:
Article