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

Umbach AT, Zhang B, Daniel C, Fajol A, Velic A, Hosseinzadeh Z, Bhavsar SK, Bock CT, Kandolf R, Pichler BJ, Amann KU, Foeller M, Lang F (2015)

Publication Type: Journal article

Publication year: 2015

Journal

Kidney International Nature Publishing Group: Open Access Hybrid Model Option A

Book Volume: 87

Pages Range: 728-37

Journal Issue: 4

DOI: 10.1038/ki.2014.371

Abstract

Calcitriol, a powerful regulator of phosphate metabolism and immune response, is generated by 25-hydroxyvitamin D 1?-hydroxylase in the kidney and macrophages. Renal 1?-hydroxylase expression is suppressed by Klotho and FGF23, the expression of which is stimulated by calcitriol. Interferon ? (INF?) regulates 1?-hydroxylase expression in macrophages through transcription factor interferon regulatory factor-1. INF?-signaling includes Janus kinase 3 (JAK3) but a role of JAK3 in the regulation of 1?-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 1?-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 1?-hydroxylase expression and phosphate transport. Its deficiency leads to marked derangement of phosphate metabolism.

Authors with CRIS profile

Christoph Daniel Department of Nephropathology Kerstin Ute Amann Department of Nephropathology

Involved external institutions

Eberhard Karls Universität Tübingen DE Germany (DE)

How to cite

APA:

Umbach, A.T., Zhang, B., Daniel, C., Fajol, A., Velic, A., Hosseinzadeh, Z.,... Lang, F. (2015). Janus kinase 3 regulates renal 25-hydroxyvitamin D 1?-hydroxylase expression, calcitriol formation, and phosphate metabolism. Kidney International, 87(4), 728-37. https://doi.org/10.1038/ki.2014.371

MLA:

Umbach, Anja T., et al. "Janus kinase 3 regulates renal 25-hydroxyvitamin D 1?-hydroxylase expression, calcitriol formation, and phosphate metabolism." Kidney International 87.4 (2015): 728-37.

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