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Project

The role of the kidney in vitamin D synthesis and vitamin D mediated calcium and phosphate handling.

Vitamin D3 has important functions in the maintenance of stable serum calcium and phosphate concentrations by pursuing a balance between intestinal absorption, bone influx and efflux and reabsorption in the kidney. In addition, the enzyme CYP27B1, responsible for the formation of the active form of vitamin D3 (1,25-dihydroxyvitamin D3 or short 1,25(OH)2D3) is mainly expressed in the kidney. Yet, CYP27B1 is also expressed in many other tissues, where it can locally synthesize 1,25(OH)2D3. Until now, it is not known whether this local production of 1,25(OH)2D3 contributes to the circulation. Hence, the first aim of this research project is to investigate the kidney’s contribution to the circulating concentration of 1,25(OH)2D3 by the use of transgenic mice with a kidney-specific deletion of the CYP27B1 enzyme. Secondly, we aim to examine the importance of vitamin D mediated signaling in the kidney on renal calcium and phosphate reabsorption. Therefore, we will use transgenic mice with a kidney-specific deletion of the vitamin D receptor (VDR), which mediates vitamin D-dependent signaling. Finally, we aim to discover new vitamin D target genes in the kidney by a combined analysis of the transcriptome after vitamin D treatment with genome wide detection of VDR binding sites.
In summary, the focus of this project is to gain more insight in the crucial role of the kidney in vitamin D3 synthesis and vitamin D3-mediated regulation of calcium and phosphate metabolism.

Date:1 Jan 2020 →  31 Dec 2023
Keywords:vitamin D3, kidney, enzym CYP27B1, calcium and phosphate handling
Disciplines:Urology and nephrology not elsewhere classified, Transcription and translation, Endocrinology, Molecular physiology