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Kidney Int. 2015 Apr;87(4):728-37. doi: 10.1038/ki.2014.371. Epub 2014 Dec 10.

Janus kinase 3 regulates renal 25-hydroxyvitamin D 1α-hydroxylase expression, calcitriol formation, and phosphate metabolism.

Author information

1
Department of Physiology, University of Tübingen, Tübingen, Germany.
2
1] Department of Physiology, University of Tübingen, Tübingen, Germany [2] Department of Molecular Pathology, University of Tübingen, Tübingen, Germany.
3
Department of Nephropathology, University Hospital Erlangen, Erlangen, Germany.
4
Proteome Center, University of Tübingen, Tübingen, Germany.
5
1] Department of Physiology, University of Tübingen, Tübingen, Germany [2] Novartis Oncology, Novartis International AG, Hyderabad, India.
6
Department of Molecular Pathology, University of Tübingen, Tübingen, Germany.
7
Department of Radiology, University of Tübingen, Tübingen, Germany.

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.

PMID:
25493954
DOI:
10.1038/ki.2014.371
[Indexed for MEDLINE]
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