Affinage

VDR

Vitamin D3 receptor · UniProt P11473

Length
427 aa
Mass
48.3 kDa
Annotated
2026-06-11
100 papers in source corpus 24 papers cited in narrative 24 extracted findings
Cross-family judge vs UniProt: tie faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

VDR is a ligand-activated nuclear receptor that, upon binding 1,25(OH)2D3, regulates transcriptional programs governing tissue homeostasis, cell-fate, metabolism, and immunity (PMID:23681781, PMID:24787735). Crystal structures of its DNA-binding domain bound to distinct response elements define an asymmetric, predominantly non-polar dimerization interface, and interface mutations generate a VDR DBD defective in homodimerization yet still able to heterodimerize, while homology modeling and mutagenesis of the ligand-binding domain identify the pincer hydrogen bonds (R274/S237 to the 1α-OH, H397 to the 25-OH) required for high-affinity ligand binding and transactivation (PMID:11980721, PMID:10828304). Reconstitution with point mutants confirms that both ligand binding (W286R, R274L) and DR3 element binding (G46D) are needed for full activity, although the partial activity of the DR3-binding mutant indicates non-canonical genomic and non-genomic signaling also contributes (PMID:23681781). Genome-wide, VDR occupies tens of thousands of sites with DR3-type direct repeats enriched at the most ligand-responsive loci, and its cistrome and outputs are shaped by chromatin accessibility set by the pioneer factor PU.1, by co-repressor recruitment (NCoR1, NCoR2/SMRT) that drives histone hypoacetylation and stable silencing of target genes, and by agonist-dependent competition with RAR for the shared partner RXR (PMID:24787735, PMID:28232093, PMID:16886664, PMID:23098689, PMID:36639026). As a transcription factor VDR both activates targets (ATG16L1, GPX4, HSD3B1, PBLD) and represses others (SOX2, NLRP6, FOXO1, SREBF1), thereby controlling intestinal autophagy and inflammation, ferroptosis resistance, steroidogenesis, macrophage M1 polarization, tumor stemness, and adipogenesis (PMID:26218741, PMID:31996668, PMID:35254654, PMID:39272040, PMID:32900990, PMID:36845152, PMID:36581217, PMID:35170865). VDR signaling restrains pathological cardiac remodeling and, when overexpressed in skeletal muscle, drives hypertrophy through mTOR-dependent translational and ribosomal expansion (PMID:26429397, PMID:32771696). VDR output is further tuned by acidosis-sensitive nuclear export, epigenetic silencing of its own promoter through DNMT3b-mediated CpG methylation, and a non-genomic mode in muscle in which 1α,25(OH)2D3 drives VDR to caveolar plasma-membrane complexes with the TRPC3 channel and Src kinase to activate second-messenger and MAPK cascades (PMID:32900990, PMID:23390308, PMID:21664245). In vivo humanized-mouse genetics establish that phosphorylation of serine 208 is dispensable for transcriptional and physiological function and that VDR in osteoclast precursors is not required for bone homeostasis (PMID:28602960, PMID:31561003).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 2002 High

    Establishing the structural basis for how VDR reads distinct response elements and selects its dimerization partner, a prerequisite for understanding target selectivity.

    Evidence X-ray crystallography of the VDR DBD on three response elements plus interface mutagenesis and in vitro heterodimerization assays

    PMID:11980721

    Open questions at the time
    • DBD structures only; full-length receptor on DNA not resolved
    • Does not address ligand-dependent conformational changes in the LBD
  2. 2000 Medium

    Defining the ligand-contact residues that confer high-affinity 1,25(OH)2D3 binding, connecting receptor chemistry to transactivation.

    Evidence Homology modeling/docking of the LBD with site-directed mutagenesis of R274, S237, H397

    PMID:10828304

    Open questions at the time
    • Model-based rather than crystallographic confirmation
    • Single lab
  3. 2013 High

    Reconstitution with separation-of-function mutants showed both ligand binding and DR3 binding are required for full VDR activity, but residual activity of a DR3-binding mutant revealed non-canonical signaling contributes to anti-cancer effects.

    Evidence Stable expression of WT and mutant hVDR (W286R, R274L, G46D) in VDR-null mammary tumor cells with proliferation and target-gene readouts

    PMID:23681781

    Open questions at the time
    • Mechanism of the non-DR3 residual signaling not defined
    • Specific to mammary tumor context
  4. 2014 High

    Genome-wide mapping established DR3 elements as the core determinant of ligand-responsive VDR occupancy while revealing the majority of sites are non-canonical.

    Evidence Unified re-analysis of six ChIP-seq datasets with de novo motif analysis

    PMID:24787735

    Open questions at the time
    • Function of non-DR3 binding sites unresolved
    • Does not assign individual sites to target genes
  5. 2017 High

    Identified pioneer-factor and tissue-level control of the VDR cistrome, showing chromatin accessibility, not direct contact, gates VDR regulatory output.

    Evidence PU.1 and VDR ChIP-seq with PU.1 knockdown in monocytes; in vivo tissue ChIP-seq and humanized S208A knock-in mice

    PMID:28232093 PMID:28602960

    Open questions at the time
    • No direct PU.1–VDR physical interaction detected
    • S208A finding is a negative result; other phosphosites not tested
  6. 2012 Medium

    Co-repressor biology was defined: NCoR1/NCoR2(SMRT) attenuate VDR activity and VDR-driven NCOR1 recruitment can seed stable epigenetic silencing of target genes.

    Evidence siRNA knockdown/overexpression of co-repressors and ChIP at IGFBP3/G0S2 promoters in prostate and breast cells, with HDAC-inhibitor co-treatment

    PMID:16886664 PMID:23098689

    Open questions at the time
    • Single lab per study
    • Causal link from transient co-repressor binding to stable DNA methylation inferred, not directly demonstrated
  7. 2011 Medium

    Demonstrated a non-genomic mode in which membrane-localized VDR couples to Ca2+ channels and kinases, expanding VDR beyond transcription.

    Evidence Subcellular fractionation, caveolae isolation, co-IP of VDR with TRPC3 and Src, and second-messenger assays in skeletal muscle cells

    PMID:21664245

    Open questions at the time
    • Single lab; reciprocal Co-IP validation limited
    • Stoichiometry and direct vs. scaffolded interaction with TRPC3/Src unclear
  8. 2015 Medium

    Linked VDR to intestinal autophagy and host-microbe homeostasis through direct transcriptional activation of ATG16L1.

    Evidence Reporter assays, VDR knockdown, ChIP, and a mouse colitis model with butyrate modulation

    PMID:26218741

    Open questions at the time
    • Single lab
    • Does not resolve VDRE location specificity at the ATG16L1 locus
  9. 2020 High

    Established VDR as a regulator of ferroptosis and tumor stemness via opposing transcriptional outputs, and showed acidosis controls VDR localization.

    Evidence Luciferase/ChIP-seq/ATAC-seq with VDR knockout mice, siRNA, and in vivo AKI and CRC models linking VDR to GPX4 activation and SOX2 repression

    PMID:31996668 PMID:32900990

    Open questions at the time
    • Mechanism of acidosis sensing by the nuclear export signal not detailed
    • Generalizability of GPX4/SOX2 regulation across tissues untested
  10. 2020 Medium

    Showed VDR drives skeletal muscle hypertrophy through mTOR-dependent translational and ribosomal programs, and restrains pathological cardiac remodeling.

    Evidence In vivo VDR electrotransfer overexpression with D2O tracer MPS and RNA-Seq in rat muscle (corroborated in humans); VDR-/- × MHC-DGAT1 cardiac epistasis with echocardiography

    PMID:26429397 PMID:32771696

    Open questions at the time
    • Direct VDR transcriptional targets driving muscle mTOR signaling not pinpointed
    • Cardiac protection mechanism inferred from epistasis, not defined molecularly
  11. 2023 Medium

    Defined receptor competition for RXR as a layer of VDR regulation, with RAR dominating partner occupancy in an agonist-dependent manner.

    Evidence Fluorescence correlation spectroscopy in live cells co-expressing RAR/VDR/RXR under defined agonist conditions

    PMID:36639026

    Open questions at the time
    • No structural or in vitro reconstitution of competition
    • Single lab
  12. 2024 Medium

    Extended VDR's repertoire to immune and metabolic programs, including macrophage M1 polarization (PBLD, JAK1/STAT1), β-cell ferroptosis via FOXO1, steroidogenesis via HSD3B1, NLRP6 inflammasome repression, and adipogenesis via the miR-122/VDR/SREBF1 axis.

    Evidence ChIP/ChIP-seq/ATAC-seq, dual-luciferase, reciprocal siRNA, proteomics, target-engagement assays, and myeloid-specific or global VDR knockout mouse models across multiple tissues

    PMID:35170865 PMID:35254654 PMID:36581217 PMID:36845152 PMID:37633235 PMID:39272040

    Open questions at the time
    • Mostly single-lab studies per target
    • Whether these targets are conserved direct VDR effectors across human tissues untested
  13. 2013 Medium

    Showed VDR expression is itself epigenetically silenced, providing a route for disease (HIV) to suppress VDR-dependent protection.

    Evidence Bisulfite methylation analysis, DNMT3b measurement, and AZA reversal with RAS/ROS/DSB and apoptosis readouts in HIV-infected T cells

    PMID:23390308

    Open questions at the time
    • Single lab
    • Direct DNMT3b recruitment to the VDR promoter not demonstrated

Open questions

Synthesis pass · forward-looking unresolved questions
  • The function of the predominant non-DR3 VDR binding sites and how ligand-, chromatin-, co-regulator-, and localization-based inputs are integrated into tissue-specific transcriptional outcomes remain unresolved.
  • No full-length VDR–RXR–DNA structure in the timeline
  • Functional annotation of non-canonical binding sites missing
  • Unified model reconciling genomic and non-genomic signaling absent

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 7 GO:0003677 DNA binding 3 GO:0008289 lipid binding 2
Localization
GO:0005634 nucleus 3 GO:0005886 plasma membrane 1
Pathway
R-HSA-168256 Immune System 3 R-HSA-5357801 Programmed Cell Death 2 R-HSA-74160 Gene expression (Transcription) 2 R-HSA-162582 Signal Transduction 1
Partners
NCOR1NCOR2PU.1RARRXRSRCTRPC3
Complex memberships
VDR-RXR heterodimercaveolar VDR-TRPC3-Src membrane complex

Evidence

Reading pass · 24 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2002 Crystal structures of the VDR DNA-binding domain (DBD) at 2.7–2.8 Å resolution in complex with three different response elements (osteopontin SPP, canonical DR3, and osteocalcin OC) revealed the chemical basis for differential affinity at distinct response elements. The homodimeric protein-protein interface is stabilized by van der Waals interactions and is predominantly non-polar. Structure-based mutations in the asymmetric homodimeric interface created a VDR DBD defective in homodimerization but capable of heterodimerization with the RXR DBD, defining the dimerization interface. X-ray crystallography (2.7–2.8 Å), structure-based site-directed mutagenesis, in vitro heterodimerization assay The EMBO journal High 11980721
2000 Homology modeling of the VDR ligand-binding domain (LBD) with docking of 1,25-(OH)2D3 identified specific hydrogen-bond interactions: the 1α-OH group forms a pincer-type hydrogen bond with R274 and S237, and the 25-OH group contacts H397. Mutation analysis confirmed these residues are required for high-affinity ligand binding and transactivation. Homology modeling, docking simulation, site-directed mutagenesis Current pharmaceutical design Medium 10828304
2011 In skeletal muscle cells, 1α,25(OH)2D3 induces rapid non-genomic signaling via the VDR. Short-term 1α,25(OH)2D3 treatment causes reverse translocation of VDR from nucleus to plasma membranes, where it forms a complex in caveolae with TRPC3 (a capacitative Ca2+ entry channel). VDR also forms complexes with Src kinase, linking it to MAPK cascade activation. These events stimulate adenylyl cyclase/cAMP/PKA, PLC/DAG+IP3/PKC, Ca2+ messenger, and MAPK pathways. Subcellular fractionation, co-immunoprecipitation, caveolae isolation, second-messenger assays Molecular and cellular endocrinology Medium 21664245
2015 VDR transcriptionally regulates ATG16L1 as a direct target gene. Low intestinal VDR levels are associated with abnormal Paneth cells, impaired autophagy, and dysbiosis with reduced ATG16L1 expression. Butyrate increases intestinal VDR expression and suppresses inflammation in a colitis model. Transcriptional reporter assays, VDR knockdown, mouse colitis model, ChIP Autophagy Medium 26218741
2020 VDR activation protects against cisplatin-induced acute kidney injury by inhibiting ferroptosis. Mechanistically, VDR transcriptionally activates GPX4 (a key regulator of ferroptosis), as confirmed by luciferase reporter assay. VDR knockout mice showed markedly increased ferroptotic cell death and worse kidney injury. siRNA knockdown of GPX4 largely abolished the protective effect of VDR agonist paricalcitol. Luciferase reporter assay, VDR knockout mouse, siRNA knockdown, ferroptosis phenotype assays (lipid peroxidation, MDA, 4-HNE measurement), in vivo cisplatin AKI model Cell death & disease High 31996668
2020 In an acidic tumor microenvironment, VDR is exported from the nucleus (its nuclear export signal is sensitive to acidosis), reducing its transcriptional activity. VDR directly binds to vitamin D response elements (VDREs) in the SOX2 promoter and transcriptionally represses SOX2, as shown by ChIP-seq and ATAC-seq. Loss of nuclear VDR in acidosis allows SOX2 upregulation, increasing colorectal cancer stemness and drug resistance. ChIP-seq, ATAC-seq, nuclear export signal analysis, VDR overexpression, SOX2 reporter assays, in vivo mouse CRC model Signal transduction and targeted therapy High 32900990
2020 Overexpression of VDR in rat tibialis anterior muscle in vivo via electrotransfer increased myofibre area (hypertrophy), total protein and RNA accretion, mTOR signaling (translational efficiency), ribosomal expansion, satellite cell content, and extracellular matrix remodelling gene-sets, with no effects on protein breakdown markers. RNA-Seq identified downstream transcriptional programs. VDR expression correlated with hypertrophy in humans after resistance exercise training. In vivo electrotransfer VDR overexpression in rat muscle, stable isotope tracer (D2O) MPS measurement, RNA-Seq, human resistance exercise training transcriptomics Molecular metabolism High 32771696
2014 Genome-wide ChIP-seq analysis across six cellular models identified 23,409 non-overlapping VDR binding sites. De novo motif analysis showed that direct repeat sequences spaced by 3 nucleotides (DR3-type) are preferentially enriched at highly ligand-responsive VDR loci across all cell types, indicating that DR3 elements are a core determinant of VDR occupancy and ligand responsiveness. The majority of VDR binding sites do not contain a DR3 sequence, suggesting widespread non-canonical binding. ChIP-seq (six datasets), MACS peak calling, de novo motif analysis, HOMER screening PloS one High 24787735
2017 The pioneer transcription factor PU.1 modulates VDR signaling genome-wide in human monocytes. 1,25(OH)2D3 significantly increased PU.1 binding at 6,498 genomic loci that overlap with VDR sites. PU.1 knockdown altered transcriptional activation of 1,25(OH)2D3 target genes. Chromatin accessibility at PU.1 sites was the major discriminator of regulatory outcomes. No direct physical interaction between PU.1 and VDR was detected. ChIP-seq (PU.1 and VDR cistrome mapping), PU.1 siRNA knockdown, chromatin accessibility analysis, 1,25(OH)2D3 treatment of THP-1 monocytes Biochimica et biophysica acta. Gene regulatory mechanisms Medium 28232093
2006 Elevated co-repressors NCoR2/SMRT (in prostate cancer) and NCoR1 (in breast cancer) attenuate VDR transcriptional and anti-proliferative responses to 1α,25(OH)2D3. siRNA knockdown of NCoR2/SMRT in prostate cancer cells restored VDR transcriptional activity and anti-proliferative responses. Overexpression of NCoR1 in non-malignant breast epithelial cells suppressed VDR actions. Co-treatment with HDAC inhibitors (TSA, NaB) plus 1α,25(OH)2D3 synergistically induced GADD45α and p21waf1/cip1 and inhibited proliferation. siRNA knockdown of co-repressors, NCoR1 overexpression, proliferation assays, gene expression assays, co-treatment experiments in primary tumor material and cell lines Anticancer research Medium 16886664
2012 In prostate cancer cells (PC-3), VDR inappropriately recruits the co-repressor NCOR1 to the promoter regions of target genes IGFBP3 and G0S2. ChIP assays showed that VDR-induced NCOR1 enrichment at VDR-binding regions correlates with suppressed transcriptional responses and local H3K9 hypoacetylation, proposing a mechanism by which transient co-repressor binding triggers stable DNA methylation-based silencing. Chromatin immunoprecipitation (ChIP), time-resolved gene expression analysis, comparison between non-malignant RWPE-1 and PC-3 prostate cells The Journal of steroid biochemistry and molecular biology Medium 23098689
2013 Stable expression of wild-type human VDR in VDR-knockout murine mammary tumor cells restored 1,25D-induced growth inhibition and target gene regulation (PDGFB, VEGFA, NFKBI). VDR point mutations W286R and R274L (reducing/abolishing ligand binding) abolished responses at physiological doses. VDR mutation G46D (abrogating DR3 binding) provided only partial growth inhibition, demonstrating that non-canonical (non-DR3) genomic or non-genomic VDR signaling contributes to anti-cancer effects. Stable transfection of WT and mutant hVDR into VDR-null cells, proliferation assays, gene expression analysis, site-directed mutagenesis Molecular carcinogenesis High 23681781
2017 VDR transcriptionally regulates HSD3B1 in mouse Leydig cells by binding to candidate vitamin D response elements (VDREs) in the upstream region of the Hsd3b1 gene, as confirmed by dual-luciferase reporter assay. VDR and HSD3B1 overexpression increased testosterone synthesis. HSD3B1 overexpression downregulated LPL and upregulated ANGPTL4, linking VDR→HSD3B1 to lipid metabolism regulation in Leydig cells. Dual-luciferase reporter assay, VDR deletion (testicular proteome data), VDR and HSD3B1 overexpression, RT-qPCR, western blot, testosterone ELISA Genes & genomics Medium 35254654
2022 1,25D/VDR inhibits ferroptosis in pancreatic β cells by downregulating the transcription factor FOXO1. Proteomic sequencing identified FOXO1 as a downstream VDR target. VDR knockdown reversed 1,25D effects on cell viability, ROS, iron, GPX4, and ACSL4. FOXO1 knockdown independently reduced β cell ferroptotic death, phenocopying VDR activation. Proteomic sequencing (identifying FOXO1 as VDR target), VDR siRNA knockdown, FOXO1 siRNA knockdown, ROS and iron assays, western blot for GPX4/ACSL4, STZ-induced T2DM rat model Cellular signalling Medium 36581217
2023 VDR transcriptionally represses NLRP6 in intestinal epithelial cells by binding to VDREs in the NLRP6 promoter, as demonstrated by ChIP and ATAC-seq. VD3-mediated VDR activation abolished NLRP6 inflammasome assembly (suppressing NLRP6, ASC, and Caspase-1), with protective effects against ulcerative colitis confirmed in NLRP6-/- mice and siRNA-NLRP6 cells. ChIP assay, ATAC-seq, VDR agonist treatment, NLRP6 knockout mice, siRNA knockdown, RNA-seq, colitis mouse model Frontiers in immunology High 36845152
2023 RAR and VDR compete for heterodimerization with their shared partner RXR in live cells in an agonist-dependent manner, and this competition is manifested in their DNA binding. Fluorescence correlation spectroscopy showed that coexpression of RAR and VDR with RXR leads to reduced DNA-bound fraction of each receptor when the other's agonist is present. RAR dominates over VDR for RXR binding in the absence of agonist or when both agonists are present. RXR agonist increases RAR DNA binding at the expense of VDR. Fluorescence correlation spectroscopy (FCS) in live cells, agonist treatment, co-expression of RAR/VDR/RXR The Journal of biological chemistry Medium 36639026
2024 Vitexin directly binds the VDR protein and facilitates VDR nuclear translocation to exert transcriptional activity. ChIP-seq and dual-luciferase reporter assays established that VDR transcriptionally activates PBLD (phenazine biosynthesis-like domain protein) via VDREs in its promoter. VDR/PBLD signaling promotes M1 macrophage polarization. In myeloid-specific VDR knockout mice, the protective effects of vitexin on colitis-associated colorectal cancer were abolished. Molecular docking, co-culture macrophage/cancer cell model, ChIP-seq, dual-luciferase reporter assay, VDR nuclear translocation imaging, myeloid-specific VDR KO mouse model Molecular cancer High 39272040
2023 Monotropein binds the VDR protein directly (confirmed by molecular docking, biolayer interferometry BLI, CESTA, and DARTS). VDR nuclear translocation is reduced in tumor-conditioned macrophages, and monotropein treatment restores nuclear VDR, activates VDR signaling, and promotes M1 macrophage polarization via the VDR/JAK1/STAT1 pathway. Normal and myeloid VDR knockout mice confirmed JAK1 upregulation and M1 polarization downstream of VDR. Molecular docking, BLI, CESTA, DARTS (target engagement), immunofluorescence for VDR localization, VDR knockout animals, western blot for JAK1/STAT1, macrophage polarization assays International immunopharmacology Medium 37633235
2017 In vivo ChIP-seq from mouse tissues identified tissue-specific regulatory regions controlling Vdr gene expression. A humanized VDR mouse expressing hVDR with a S208A mutation (serine 208 → alanine, abolishing phosphorylation at that site) showed unchanged target gene expression, normal serum calcium and PTH, and no alopecia, establishing that phosphorylation of hVDR at serine 208 is NOT required for transcriptional activity or in vivo function. ChIP-seq in mouse tissues, transgenic humanized VDR mouse models (mini-gene), hVDR-S208A knock-in mice, target gene expression, serum biochemistry The Journal of steroid biochemistry and molecular biology High 28602960
2019 Conditional deletion of Vdr specifically in myeloid cells (osteoclast precursors, monocytes, macrophages) did not alter bone or calcium homeostasis under normal or low-calcium diet conditions, and osteoclastogenesis from Vdr-null myeloid cells was equivalent to wildtype. This establishes that VDR signaling in osteoclast precursors is NOT required for bone homeostasis. Myeloid-specific Vdr conditional knockout (M-lysozyme-Cre), bone densitometry, calcium homeostasis measurements, in vitro osteoclastogenesis assay (M-CSF/RANKL, osteoblast co-culture), dietary calcium restriction challenge The Journal of steroid biochemistry and molecular biology High 31561003
2021 In C. elegans, the VDR ortholog DAF-12 acts cell-autonomously in specific cell types to control anatomical, molecular, and behavioral remodeling during dauer entry. Conditional alleles showed that DAF-12/VDR is required continuously both to initiate and maintain tissue remodeling (not only at entry). DAF-12/VDR also exhibits non-cell-autonomous function in nervous system remodeling, indicating interorgan signaling. Conditional genetic alleles (spatial and temporal control), tissue-specific rescue experiments, behavioral and anatomical phenotyping in C. elegans dauer model PLoS biology Medium 33891586
2022 miR-122 directly targets VDR mRNA (confirmed by dual-luciferase reporter assay). VDR in turn binds to the BS1 region of the SREBF1 promoter and inhibits SREBF1 expression (confirmed by ChIP). The miR-122/VDR/SREBF1 axis regulates adipogenesis: VDR overexpression inhibits adipogenesis, while exosomal miR-122 reverses this inhibition by suppressing VDR, thereby derepressing SREBF1 and promoting lipid accumulation. Dual-luciferase reporter assay (miR-122 targeting VDR 3'UTR), ChIP (VDR binding SREBF1 promoter), VDR overexpression, miR-122 inhibition, high-fat diet mouse model Obesity (Silver Spring, Md.) Medium 35170865
2015 In a murine model of cardiac steatosis (MHC-DGAT1 transgenic mice), VDR deficiency (VDR-/- background) synergistically worsened cardiomyopathy: double-mutant mice showed greater myocyte hypertrophy, increased interstitial fibrosis (collagen 1a1, collagen 3a1, osteopontin, MMP2 upregulation), and severely reduced ejection fraction (37% reduction) and fractional shortening (55% reduction) compared to either single mutant alone, establishing that VDR signaling restrains pathological cardiac remodeling. VDR-/- × MHC-DGAT1 Tg genetic cross, echocardiography (ejection fraction, fractional shortening), histology (fibrosis), gene expression (collagen, natriuretic peptide, ECM genes) The Journal of steroid biochemistry and molecular biology Medium 26429397
2013 HIV infection of T cells induces VDR promoter CpG methylation via upregulation of DNMT3b, resulting in attenuated VDR expression. This epigenetic silencing activates RAS, increases ROS generation, and induces DNA double-strand breaks, leading to T cell apoptosis. Demethylating agent 5-azacytidine (AZA) reversed VDR hypermethylation and blocked HIV-induced T cell apoptosis. Bisulfite methylation analysis, DNMT3b expression measurement, demethylating agent (AZA) treatment, RAS activation assay, ROS/DSB quantification, apoptosis assays Journal of leukocyte biology Medium 23390308

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2009 The relevance of vitamin D receptor (VDR) gene polymorphisms for cancer: a review of the literature. Anticancer research 248 19667145
2020 VDR activation attenuate cisplatin induced AKI by inhibiting ferroptosis. Cell death & disease 239 31996668
2005 Expression of VDR and CYP24A1 mRNA in human tumors. Cancer chemotherapy and pharmacology 191 16180015
2022 Vitamin D Receptor (VDR) Gene Polymorphisms Modify the Response to Vitamin D Supplementation: A Systematic Review and Meta-Analysis. Nutrients 126 35057541
2014 Patterns of genome-wide VDR locations. PloS one 112 24787735
2006 Evolution and function of the NR1I nuclear hormone receptor subfamily (VDR, PXR, and CAR) with respect to metabolism of xenobiotics and endogenous compounds. Current drug metabolism 107 16724925
2018 Ancient Nuclear Receptor VDR With New Functions: Microbiome and Inflammation. Inflammatory bowel diseases 104 29718408
2010 Evolution of promiscuous nuclear hormone receptors: LXR, FXR, VDR, PXR, and CAR. Molecular and cellular endocrinology 101 20615451
2002 Structural basis of VDR-DNA interactions on direct repeat response elements. The EMBO journal 99 11980721
2016 The role of vitamin D and VDR in carcinogenesis: Through epidemiology and basic sciences. The Journal of steroid biochemistry and molecular biology 98 27913313
2024 Discovery of vitexin as a novel VDR agonist that mitigates the transition from chronic intestinal inflammation to colorectal cancer. Molecular cancer 94 39272040
2017 Vitamin D and Autoimmune Diseases: Is Vitamin D Receptor (VDR) Polymorphism the Culprit? The Israel Medical Association journal : IMAJ 90 28786260
2007 Therapeutic implications of the TLR and VDR partnership. Trends in molecular medicine 88 17276732
2015 VDR/vitamin D receptor regulates autophagic activity through ATG16L1. Autophagy 87 26218741
2022 The Vitamin D/Vitamin D receptor (VDR) axis in muscle atrophy and sarcopenia. Cellular signalling 85 35595176
2020 Overexpression of the vitamin D receptor (VDR) induces skeletal muscle hypertrophy. Molecular metabolism 84 32771696
2013 LncRNA profiling reveals new mechanism for VDR protection against skin cancer formation. The Journal of steroid biochemistry and molecular biology 81 24342142
2017 Vitamin D/VDR, Probiotics, and Gastrointestinal Diseases. Current medicinal chemistry 80 27915988
2009 The yin and yang of vitamin D receptor (VDR) signaling in neoplastic progression: operational networks and tissue-specific growth control. Biochemical pharmacology 80 19737544
2006 Polymorphisms in the MTHFR and VDR genes and skin cancer risk. Carcinogenesis 77 16950800
2011 VDR activation of intracellular signaling pathways in skeletal muscle. Molecular and cellular endocrinology 76 21664245
2014 Decreased VDR expression in cutaneous melanomas as marker of tumor progression: new data and analyses. Anticancer research 73 24922634
2018 Role of vitamin D and vitamin D receptor (VDR) in oral cancer. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 70 30399574
2015 Association between vitamin D receptor (VDR) gene polymorphisms and systemic lupus erythematosus in Portuguese patients. Lupus 67 25661837
2004 Haplotype analysis of VDR gene polymorphisms: a meta-analysis. Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA 62 15057510
2006 BsmI, TaqI, ApaI and FokI polymorphisms in the vitamin D receptor (VDR) gene and the risk of osteoporosis: a meta-analysis. Disease markers 58 17264402
2009 SNAI1 expression in colon cancer related with CDH1 and VDR downregulation in normal adjacent tissue. Oncogene 56 19802011
2017 Vitamin D and VDR in Gynecological Cancers-A Systematic Review. International journal of molecular sciences 55 29113037
2010 VDR microRNA expression and epigenetic silencing of vitamin D signaling in melanoma cells. The Journal of steroid biochemistry and molecular biology 54 20153427
2002 Analysis of vitamin D-receptor (VDR) and retinoid X-receptor alpha in breast cancer. The Histochemical journal 54 12365798
2016 Crosstalk between Vitamin D Metabolism, VDR Signalling, and Innate Immunity. BioMed research international 53 27403416
2014 Novel mechanisms for the vitamin D receptor (VDR) in the skin and in skin cancer. The Journal of steroid biochemistry and molecular biology 53 25445917
2020 VDR-SOX2 signaling promotes colorectal cancer stemness and malignancy in an acidic microenvironment. Signal transduction and targeted therapy 52 32900990
2013 Vitamin D receptor (VDR) polymorphisms and severe RSV bronchiolitis: a systematic review and meta-analysis. Pediatric pulmonology 51 24019226
2008 Vitamin D receptor (VDR) gene polymorphisms and Graves' disease: a meta-analysis. Clinical endocrinology 51 18782354
2017 Fine tuning of vitamin D receptor (VDR) activity by post-transcriptional and post-translational modifications. Oncotarget 50 28427151
2010 BsmI, TaqI, ApaI and FokI polymorphisms in the vitamin D receptor (VDR) gene and risk of fracture in Caucasians: a meta-analysis. Bone 50 20601302
2013 Relationship between vitamin D receptor gene (VDR) polymorphisms, vitamin D status, osteoarthritis and intervertebral disc degeneration. The Journal of steroid biochemistry and molecular biology 44 23500379
2006 Epigenetic corruption of VDR signalling in malignancy. Anticancer research 44 16886664
2005 Vitamin-D receptor (VDR) gene (Fok-I, Taq-I and Apa-I) polymorphisms in healthy individuals from north Indian population. Asian Pacific journal of cancer prevention : APJCP 44 16101324
1998 Localization of 1,25-dihydroxyvitamin D3 receptor (VDR) expression in human prostate. The Journal of steroid biochemistry and molecular biology 44 9719446
2023 VDR Gene Single Nucleotide Polymorphisms and Autoimmunity: A Narrative Review. Biology 43 37508347
2019 Association between vitamin D receptor (VDR) polymorphisms and the risk of multiple sclerosis (MS): an updated meta-analysis. BMC neurology 40 31878897
2018 Adipose tissue inflammation and VDR expression and methylation in colorectal cancer. Clinical epigenetics 40 29719581
2017 VDR Gene variation and insulin resistance related diseases. Lipids in health and disease 39 28822353
2017 Vitamin D and VDR in cancer cachexia and muscle regeneration. Oncotarget 37 28423519
2007 Identification of VDR-responsive gene signatures in breast cancer cells. Oncology 37 17377416
2009 Cross-talk between vitamin D receptor (VDR)- and peroxisome proliferator-activated receptor (PPAR)-signaling in melanoma cells. Anticancer research 36 19667161
2022 Exosomal miR-122 promotes adipogenesis and aggravates obesity through the VDR/SREBF1 axis. Obesity (Silver Spring, Md.) 34 35170865
2017 Epigenomic PU.1-VDR crosstalk modulates vitamin D signaling. Biochimica et biophysica acta. Gene regulatory mechanisms 34 28232093
2013 Vitamin D action: lessons from VDR and Cyp27b1 null mice. Pediatric endocrinology reviews : PER 34 23858619
2022 1,25D/VDR inhibits pancreatic β cell ferroptosis by downregulating FOXO1 expression in diabetes mellitus. Cellular signalling 33 36581217
2020 Vitamin D receptor (VDR) and metabolizing enzymes CYP27B1 and CYP24A1 in breast cancer. Molecular biology reports 33 33259013
2021 DAF-16/FoxO and DAF-12/VDR control cellular plasticity both cell-autonomously and via interorgan signaling. PLoS biology 30 33891586
2020 Vitamin D receptor (VDR) gene polymorphism and risk of rheumatoid arthritis (RA): systematic review and meta-analysis. Clinical rheumatology 30 32445089
2013 Polymorphisms in the vitamin D Receptor (VDR) and the risk of ovarian cancer: a meta-analysis. PloS one 29 23826116
2019 VDR Gene Polymorphisms and Allergic Diseases: Evidence from a Meta-analysis. Immunological investigations 28 31752548
2015 NRAMP1 and VDR Gene Polymorphisms in Susceptibility to Tuberculosis in Venezuelan Population. Disease markers 28 26578819
2017 Vitamin D receptor (VDR) polymorphisms are associated to spontaneous preterm birth and maternal aspects. Gene 27 29128634
2020 Characterization of VDR and CYP27B1 expression in the endometrium during the menstrual cycle before embryo transfer: implications for endometrial receptivity. Reproductive biology and endocrinology : RB&E 26 32183826
2014 Polymorphisms in the vitamin D receptor (VDR) genes and skin cancer risk in European population: a meta-analysis. Archives of dermatological research 26 24771013
2017 The regulatory role of miRNAs on VDR in breast cancer. Transcription 25 28598255
2017 The impact of VDR expression and regulation in vivo. The Journal of steroid biochemistry and molecular biology 25 28602960
2015 Expression of Vitamin D Receptor (VDR) Positively Correlates with Survival of Urothelial Bladder Cancer Patients. International journal of molecular sciences 24 26501255
2021 Evaluation of expression of VDR-associated lncRNAs in COVID-19 patients. BMC infectious diseases 23 34147082
2013 VDR hypermethylation and HIV-induced T cell loss. Journal of leukocyte biology 23 23390308
2000 Structure-function analysis of vitamin D and VDR model. Current pharmaceutical design 23 10828304
2023 Monotropein inhibits colitis associated cancer through VDR/JAK1/STAT1 regulation of macrophage polarization. International immunopharmacology 22 37633235
2020 Cytoplasmic VDR expression as an independent risk factor for ovarian cancer. Histochemistry and cell biology 22 32572587
2024 Role of Calcitriol and Vitamin D Receptor (VDR) Gene Polymorphisms in Alzheimer's Disease. International journal of molecular sciences 21 38732025
2016 Association Between VDR FokI Polymorphism and Intervertebral Disk Degeneration. Genomics, proteomics & bioinformatics 21 26772150
2021 Promoter hypermethylation regulates vitamin D receptor (VDR) expression in colorectal cancer-A study from Kashmir valley. Cancer genetics 20 33486463
2021 Vitamin D Receptor (VDR) Gene Polymorphisms and Risk of Coronary Artery Disease (CAD): Systematic Review and Meta-analysis. Biochemical genetics 20 33590380
2020 New perspectives on PPAR, VDR and FXRα as new actors in testicular pathophysiology. Molecular aspects of medicine 20 32878696
2023 Role of the Vitamin D Receptor (VDR) in the Pathogenesis of Osteoporosis: A Genetic, Epigenetic and Molecular Pilot Study. Genes 19 36980815
2013 Vitamin D receptor gene (VDR) polymorphisms and the urolithiasis risk: an updated meta-analysis based on 20 case-control studies. Urolithiasis 19 24190699
2012 ApaI, BsmI, FokI and TaqI polymorphisms in the vitamin D receptor (VDR) gene and the risk of psoriasis: a meta-analysis. Journal of the European Academy of Dermatology and Venereology : JEADV 19 22540341
2023 Vitamin D3 alleviates inflammation in ulcerative colitis by activating the VDR-NLRP6 signaling pathway. Frontiers in immunology 18 36845152
2022 Vitamin D Receptor (VDR) Genetic Variants: Relationship of FokI Genotypes with VDR Expression and Clinical Disease Activity in Systemic Lupus Erythematosus Patients. Genes 18 36360253
2021 Vitamin D Receptor (VDR) Gene Polymorphism in Patients Diagnosed with Colorectal Cancer. Nutrients 18 33440610
2017 VDR gene methylation as a molecular adaption to light exposure: Historic, recent and genetic influences. American journal of human biology : the official journal of the Human Biology Council 18 28432711
2013 Vitamin D Receptor (VDR) Polymorphisms and Late-Onset Alzheimer's Disease: An Association Study. Iranian journal of public health 18 26171337
2020 The Correlation Between Vitamin D Receptor (VDR) Gene Polymorphisms and Autism: A Meta-analysis. Journal of molecular neuroscience : MN 17 31900887
2015 Amplification of lipotoxic cardiomyopathy in the VDR gene knockout mouse. The Journal of steroid biochemistry and molecular biology 17 26429397
2013 Vitamin D receptor (VDR) gene polymorphisms and age onset in type 1 diabetes mellitus. Autoimmunity 17 23721405
2023 Agonist-controlled competition of RAR and VDR nuclear receptors for heterodimerization with RXR is manifested in their DNA binding. The Journal of biological chemistry 16 36639026
2019 Association of VDR and OPG gene polymorphism with osteoporosis risk in Chinese postmenopausal women. Climacteric : the journal of the International Menopause Society 16 30624097
2015 Association of vdr, cyp27b1, cyp24a1 and mthfr gene polymorphisms with oral lichen planus risk. Clinical oral investigations 16 26303648
2013 Stable expression of human VDR in murine VDR-null cells recapitulates vitamin D mediated anti-cancer signaling. Molecular carcinogenesis 16 23681781
2022 Synergistic autophagy blockade and VDR signaling activation enhance stellate cell reprogramming in pancreatic ductal adenocarcinoma. Cancer letters 15 35526650
2010 Peroxisome proliferator-activated receptor (PPAR) and vitamin D receptor (VDR) signaling pathways in melanoma cells: promising new therapeutic targets? The Journal of steroid biochemistry and molecular biology 15 20214982
2023 Vitamin D receptor (VDR) mediates the quiescence of activated hepatic stellate cells (aHSCs) by regulating M2 macrophage exosomal smooth muscle cell-associated protein 5 (SMAP-5). Journal of Zhejiang University. Science. B 14 36916000
2019 Vitamin D receptor (VDR) gene polymorphism and osteoporosis risk in White British men. Annals of human biology 14 31448632
2019 Vdr expression in osteoclast precursors is not critical in bone homeostasis. The Journal of steroid biochemistry and molecular biology 14 31561003
2015 Regulation of VDR Expression in Apc-Mutant Mice, Human Colon Cancers and Adenomas. Cancer prevention research (Philadelphia, Pa.) 14 25873367
2012 Epigenetic distortion to VDR transcriptional regulation in prostate cancer cells. The Journal of steroid biochemistry and molecular biology 14 23098689
2022 VDR mediated HSD3B1 to regulate lipid metabolism and promoted testosterone synthesis in mouse Leydig cells. Genes & genomics 13 35254654
2022 Vitamin D3 eradicates Helicobacter pylori by inducing VDR-CAMP signaling. Frontiers in microbiology 13 36569092
2021 FokI polymorphism of the vitamin D receptor (VDR) gene and susceptibility to tuberculosis: Evidence through a meta-analysis. Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases 13 33901685
2018 Reduced vitamin D receptor (VDR) expression and plasma vitamin D levels are associated with aging-related prostate lesions. The Prostate 13 29508414

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