Cytosolic sequestration of the vitamin D receptor as a therapeutic option for vitamin D-induced hypercalcemia.

ABSTRACT: The bioactive vitamin D₃, 1α,25(OH)₂D₃, plays a central role in calcium homeostasis by controlling the activity of the vitamin D receptor (VDR) in various tissues. Hypercalcemia secondary to high circulating levels of vitamin D₃ leads to hypercalciuria, nephrocalcinosis and renal dysfunctions. Current therapeutic strategies aim at limiting calcium intake, absorption and resorption, or 1α,25(OH)₂D₃ synthesis, but are poorly efficient. In this study, we identify WBP4 as a new VDR interactant, and demonstrate that it controls VDR subcellular localization. Moreover, we show that the vitamin D analogue ZK168281 enhances the interaction between VDR and WBP4 in the cytosol, and normalizes the expression of VDR target genes and seru

SUBMITTER: Rovito D 

PROVIDER: S-EPMC7721737 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature