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Janus kinase 3 regulates renal 25-hydroxyvitamin D 1α-hydroxylase expression, calcitriol formation, and phosphate metabolism
- Source :
- Kidney International. 87:728-737
- Publication Year :
- 2015
- Publisher :
- Elsevier BV, 2015.
-
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.
- Subjects :
- Male
Calbindins
medicine.medical_specialty
Calcitriol
Xenopus
Biology
Kidney
Sodium-Phosphate Cotransporter Proteins, Type IIa
Phosphates
Feces
Mice
chemistry.chemical_compound
Interferon
Internal medicine
medicine
Animals
RNA, Messenger
Intestinal Mucosa
Klotho
Transcription factor
25-Hydroxyvitamin D3 1-alpha-Hydroxylase
Mice, Knockout
Janus kinase 3
Janus Kinase 3
Phosphate
Up-Regulation
Fibroblast Growth Factors
Fibroblast Growth Factor-23
Endocrinology
medicine.anatomical_structure
chemistry
Nephrology
Oocytes
Female
Renal phosphate excretion
Interferon Regulatory Factor-1
medicine.drug
Subjects
Details
- ISSN :
- 00852538
- Volume :
- 87
- Database :
- OpenAIRE
- Journal :
- Kidney International
- Accession number :
- edsair.doi.dedup.....f35aed06d12d35ab0bcbb9151f21e874
- Full Text :
- https://doi.org/10.1038/ki.2014.371