Skip to Main content Skip to Navigation
Journal articles

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 serum calcium levels in 1α,25(OH)2D3-intoxicated mice. As ZK168281 also blunts 1α,25(OH)2D3-induced VDR signaling in fibroblasts of a patient with impaired vitamin D degradation, this VDR antagonist represents a promising therapeutic option for 1α,25(OH)2D3-induced hypercalcemia.
Complete list of metadata

https://hal-normandie-univ.archives-ouvertes.fr/hal-03193197
Contributor : Erika Hue <>
Submitted on : Thursday, April 8, 2021 - 3:53:41 PM
Last modification on : Thursday, April 15, 2021 - 5:26:22 PM

File

41467_2020_Article_20069.pdf
Publisher files allowed on an open archive

Identifiers

Citation

Daniela Rovito, Anna Belorusova, Sandra Chalhoub, Anna-Isavella Rerra, Elvire Guiot, et al.. Cytosolic sequestration of the vitamin D receptor as a therapeutic option for vitamin D-induced hypercalcemia. Nature Communications, Nature Publishing Group, 2020, 11, pp.6249. ⟨10.1038/s41467-020-20069-4⟩. ⟨hal-03193197⟩

Share

Metrics

Record views

40

Files downloads

54