Disease relevance of VDR

• Significant associations (P < 0.0125) were found between VDR and bone mineral content of the humerus at 35 weeks of age; between IGF1 and SPP1 and 5-week body weight; and between INS and 55-week body weight [1].

High impact information on VDR

• RNA selected via hybridization with this DNA sequence directed the cell-free synthesis of immunoprecipitable vitamin D3 receptor [2].
• A comparison of 1,25-dihydroxyvitamin D3 receptor concentration and equilibrium dissociation constants of whole tissue, nuclear, and cytosol extracts of vitamin D-deficient chicken intestine has been carried out [3].
• This report describes purification of a receptor for 1 alpha,25-(OH)2D3 (VDR) located in the basal-lateral membrane (BLM) of vitamin D-replete chick intestinal epithelium, which is implicated in the nongenomic stimulation of calcium transport (transcaltachia) [4].
• We postulate that COUP-TF may play a master role in regulating transactivation by VDR, TR, and RAR [5].
• Instead, we show that the mechanism of repression could occur at three different levels: (a) active silencing of transcription and dual competition for; (b) occupancy of DNA binding sites; and (c), heterodimer formation with retinoid X receptor, the coregulator of VDR, TR, and RAR [5].

Biological context of VDR

• Transfection with anti-VDR antisense ODNs diminished 1alpha,25(OH)2D3-dependent Ca2+ and Mn2+ influx [6].
• The cDNA for the chicken vitamin D receptor (VDR) has been cloned in full length by screening cDNA libraries from chicken intestine and chicken kidney [7].
• Thus, in vitro and in vivo experiments do not support ligand-sensitive transactivation mediated by VDR-TR heterodimer formation but rather suggest that TR expression can repress 1,25-(OH)2D3-induced transcription predominantly by sequestering RXR [8].
• These data suggest that species specificity is a relevant aspect of VDR/VDRE recognition, and that a novel factor(s), different from VDR, might be involved in the effect of vitamin D on gene expression [9].
• Its specificity in binding structural variants of the AGGTCA repeat is broader than that of VDR, as direct repeats spaced by 3, 4, and 5 base pairs are almost equally effective competitors when added to the probe in molar excess [9].

Anatomical context of VDR

• We investigated the involvement of TRPC proteins and Vitamin D receptor (VDR) in CCE induced by 1alpha,25(OH)2D3 in chick muscle cells [6].
• This work describes the involvement of TRPC proteins in capacitative calcium entry (CCE) induced by 1alpha,25-dihydroxy-vitamin-D3 [1alpha,25(OH)2D3] in chick skeletal muscle and in rat osteoblast-like cells (ROS 17/2.8) and the role of the vitamin D receptor (VDR) in this non-genomic rapid response mediated by the hormone [10].
• However, it is able to repress hormonal induction of target genes by vitamin D3 receptor (VDR), thyroid hormone receptor (TR), and retinoic acid receptor (RAR) [5].
• Using a transient transfection system incorporating the osteocalcin VDRE (vitamin D response element) in Cos-1 cells, we found that 20 nM MK antagonizes VDR-mediated transcription by 50% when driven by 1 nM 1alpha,25(OH)2D3 [11].
• Regulation of prepro-PTH and vitamin D receptor (VDR) mRNAs in the parathyroid glands was studied in chickens in vivo [12].

Associations of VDR with chemical compounds

• The VDRE-binding activity binds DNA with high affinity and contacts it at the same guanine residues as VDR [9].
• Treatment of cultures with 36 microM cycloheximide 1 h prior to 1,25(OH)2D3 addition resulted in superinduction of VDR mRNA levels but sharply reduced CaBP steady-state mRNA levels [13].
• The CAII expression is stimulated by 1, 25-dihydroxyvitamin D(3) but not by 9-cis retinoic acid and repressed by VDR overexpression due to RXR squelching [14].
• Our results demonstrate the first retinoic acid response element in the CAII promoter and show that according to cell type, different nuclear receptors of the VDR subfamily can regulate the CAII gene [14].
• The results obtained strongly suggest that VDR in vitro can undergo gamma-carboxylation in the presence of vitamin K1 and that 15-25% of Glu residues in the VDR are carboxylated in vivo [15].

Physical interactions of VDR

• In fact, VDR-depleted CINE retains the ability to bind the rat osteocalcin VDRE [9].

Regulatory relationships of VDR

• It was found that analogs known to bind effectively to the nuclear receptor in vitro could achieve a significant occupancy of the VDR in vivo and stimulated calbindin-D28K messenger RNA and protein synthesis [16].

Other interactions of VDR

• Co-immunoprecipitation of TRPC3-like protein and VDR under non-denaturating conditions was observed [6].
• Conversely, reduced dietary calcium diminishes VDR mRNA despite increased circulating 1,25-(OH)2D3, indicating that another factor, such as parathyroid hormone, is a predominant downregulator of VDR [17].
• Lesion VDR had low affinity; Kd 83.9 +/- 20.6 pM compared to 30.0 +/- 2.8, 37.8 +/- 3.1, and 33.0 +/- 4.0 pM (p < 0.001), and low receptor number per cell, 920 +/- 74, compared to 1329 +/- 151, 1664 +/- 167, and 1360 +/- 104 (p < 0.01) in the normal proliferating, normal hypertrophic, and TD proliferating cells, respectively [18].

Analytical, diagnostic and therapeutic context of VDR

• Northern blot analysis showed that the VDR gene is expressed as a single 2.69-kb transcript in chicken intestine and kidney [7].
• Duodenal CaBP and 1,25(OH)2D3 receptor (VDR) expression were assessed by Western blot analysis, while CaBP and VDR mRNA levels were determined by Northern blot analysis [13].
• Because mature osteoclasts lack VDR, we analyzed a clonal osteoclast cell line by RT-PCR and found it contained the 1,25D(3)-MARRS mRNA [19].
• VDR expression was investigated by Western blotting analysis and the tissue distribution of the receptor was determined by immunohistochemistry [20].
• Frozen sections of the shell gland of immature, laying, and molting hens were immunostained for VDR, and the VDR in these tissues were also examined by Western blot analysis [21].

References