Janus kinase 3 regulates renal 25-hydroxyvitamin D 1α-hydroxylase expression, calcitriol formation, and phosphate metabolism.
Kidney Int
; 87(4): 728-37, 2015 Apr.
Article
em En
| MEDLINE
| ID: mdl-25493954
ABSTRACT
Calcitriol, a powerful regulator of phosphate metabolism and immune response, is generated by 25-hydroxyvitamin D 1α-hydroxylase in the kidney and macrophages. Renal 1α-hydroxylase expression is suppressed by Klotho and FGF23, the expression of which is stimulated by calcitriol. Interferon γ (INFγ) regulates 1α-hydroxylase expression in macrophages through transcription factor interferon regulatory factor-1. INFγ-signaling includes Janus kinase 3 (JAK3) but a role of JAK3 in the regulation of 1α-hydroxylase expression and mineral metabolism has not been shown. Thus, the impact of JAK3 deficiency on calcitriol formation and phosphate metabolism was measured. Renal interferon regulatory factor-1 and 1α-hydroxylase transcript levels, serum calcitriol and FGF23 levels, intestinal phosphate absorption as well as absolute and fractional renal phosphate excretion were significantly higher in jak3 knockout than in wild-type mice. Coexpression of JAK3 increased the phosphate-induced current in renal sodium-phosphate cotransporter-expressing Xenopus oocytes. Thus, JAK3 is a powerful regulator of 1α-hydroxylase expression and phosphate transport. Its deficiency leads to marked derangement of phosphate metabolism.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Fosfatos
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Calcitriol
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RNA Mensageiro
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Janus Quinase 3
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25-Hidroxivitamina D3 1-alfa-Hidroxilase
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Rim
Limite:
Animals
Idioma:
En
Revista:
Kidney Int
Ano de publicação:
2015
Tipo de documento:
Article
País de afiliação:
Alemanha