| First Author | Umbach AT | Year | 2015 |
| Journal | Kidney Int | Volume | 87 |
| Issue | 4 | Pages | 728-37 |
| PubMed ID | 25493954 | Mgi Jnum | J:319062 |
| Mgi Id | MGI:6862570 | Doi | 10.1038/ki.2014.371 |
| Citation | Umbach AT, et al. (2015) Janus kinase 3 regulates renal 25-hydroxyvitamin D 1alpha-hydroxylase expression, calcitriol formation, and phosphate metabolism. Kidney Int 87(4):728-37 |
| abstractText | Calcitriol, a powerful regulator of phosphate metabolism and immune response, is generated by 25-hydroxyvitamin D 1alpha-hydroxylase in the kidney and macrophages. Renal 1alpha-hydroxylase expression is suppressed by Klotho and FGF23, the expression of which is stimulated by calcitriol. Interferon gamma (INFgamma) regulates 1alpha-hydroxylase expression in macrophages through transcription factor interferon regulatory factor-1. INFgamma-signaling includes Janus kinase 3 (JAK3) but a role of JAK3 in the regulation of 1alpha-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 1alpha-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 1alpha-hydroxylase expression and phosphate transport. Its deficiency leads to marked derangement of phosphate metabolism. |
