VDRmediated

VDR-mediated refers to the cellular and physiological effects that are caused, or regulated, by the activation of the vitamin D receptor (VDR). VDR is a ligand-activated transcription factor in the nuclear receptor family that primarily binds 1,25-dihydroxyvitamin D3 and related secosteroids. Upon ligand binding, VDR forms a heterodimer with the retinoid X receptor (RXR) and binds to vitamin D response elements (VDREs) in the regulatory regions of target genes, modulating transcription. This genomic pathway is accompanied by recruitment of coactivator or corepressor complexes and chromatin remodeling, leading to changes in gene expression that influence calcium homeostasis, bone metabolism, immune function, and cellular differentiation.

In addition to genomic effects, VDR-mediated signaling can be involved in rapid, non-genomic responses that are less well defined. Some data point to membrane-associated forms of VDR or auxiliary proteins mediating quick signaling events that influence cell behavior without direct gene transcription changes.

Physiological relevance: In the intestine, VDR-mediated transcription increases expression of calcium transport proteins, enhancing dietary calcium absorption. In bone, VDR activity supports mineralization and remodeling. In immune cells, VDR regulates antimicrobial responses and inflammation. Clinically, VDR-based modulation has been explored for osteoporosis management, certain dermatological conditions such as psoriasis, and immune-mediated diseases, though outcomes depend on tissue context and vitamin D status.

Research and considerations: Therapeutic use requires balancing benefits with risks such as hypercalcemia or hypercalciuria. Genetic variation in the VDR gene can affect responsiveness. Experimental approaches include chromatin immunoprecipitation, transcriptomics, and VDR knockout or knock-in models to delineate direct target genes and pathways.