Current Status of Vitamin D Signaling and Its Therapeutic Applications

Abstract

Vitamin D and in particular its biologically most active metabolite, 1α,25-dihydroxyvitamin D₃ (1α,25(OH)₂D₃), are central endocrine molecules that influence many aspects of human physiology, which are not only the well-known calcium and phosphorus up-take and transport controlling bone formation, but also the control of immune functions and of cellular growth and differentiation. Basically all actions of 1α,25(OH)₂D₃ are mediated by the transcription factor vitamin D receptor (VDR). The crystal structure of the VDR and detailed knowledge on its molecular interactions with the ligand provide significant insight into the mechanisms of vitamin D signaling. This applies also on the action of the huge number of synthetic 1α,25(OH)₂D₃ analogues, which have been developed with the goal of a therapeutic application in hyper-proliferative diseases, such as psoriasis, benign prostate hyperplasia and different types of cancer, in immune functions, such as autoimmune diseases and microbial infections, or in bone disorders, such as osteoporosis. Moreover, detailed investigations on many VDR target genes and in particular the recently available genome-wide view on vitamin D signaling allows a more complete view on the potential of the nuclear hormone. In this review we discuss the latest insight into vitamin D signaling in context with the most prominent 1α,25(OH)₂D₃ analogues.

Common susceptibility variants are shared between schizophrenia and psoriasis in the Han Chinese population

“…41 Our findings therefore provide some level of validation of the potential role of calcium signalling in the etiology of schizophrenia and psoriasis. 13,42,43 …”

Role of 1α,25-Dihydroxyvitamin D3 in Adipogenesis of SGBS Cells: New Insights into Human Preadipocyte Proliferation

“…The bioactive metabolite 1,25(OH) 2 D 3 binds to the vitamin D receptor (VDR) with high affinity, acting as a pleiotropic endocrine hormone and influencing many physiological processes, including gene expression [2][3][4]. Ligand-bound VDR forms a heterodimeric complex with the retinoid-X receptor and binds to the vitamin D response element in the promoter region of target genes, thereby influencing gene expression [5,6]. In addition, vitamin D 3 exerts VDRindependent non-genomic activity by affecting intracellular signaling molecules [4,7,8].…”

The transcriptional regulator BCL6 participates in the secondary gene regulatory response to vitamin D

“…1,25(OH) 2 D 3 functions as a high affinity ligand of the transcription factor vitamin D receptor (VDR) [8]. Therefore, primary vitamin D target genes are expected to have at least one VDR binding site in relative vicinity to their transcription start site (TSS) [9].…”