Effect of Vitamin D Receptor Knockout on the Transcriptomic Landscape of Th2 Cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE285069 | GEO | 2025/12/01
REPOSITORIES: GEO
Similar Datasets
Project description:This dataset examines the transcriptional effects of vitamin D deficiency in TH2 cells isolated from Mus musculus (C57BL/6 strain). Vitamin D-deficient mice were bred and maintained under UV-free conditions with a vitamin D-depleted diet. TH2 cells from these mice (N=7) were compared to TH2 cells from wild-type mice (N=3) to assess the impact of chronic vitamin D deficiency on gene expression. RNA-seq was used to generate raw gene-level counts.
2024-11-27 | GSE283020 | GEO
Project description:This dataset profiles the transcriptional response of in vitro polarized TH2 cells treated with calcitriol (active vitamin D) and vehicle controls. RNA-seq was used to identify differentially expressed genes influenced by vitamin D signaling. This study provides insight into the molecular mechanisms through which vitamin D modulates immune responses in TH2 cells.
2024-11-27 | GSE282941 | GEO
Project description:Complex autoimmune diseases have proven difficult to dissect down to their causative genetic mechanisms. As a result, epidemiological data from different human association studies are often merged to arrive at a working hypothesis. In one of such examples, lack of sun exposure and consequent lower serum vitamin D3 levels has been proposed to increase risk of autoimmunity, attributing vitamin D3 an immune regulatory role. However, conclusive evidence demonstrating its efficacy in treating autoimmune diseases is missing. In this study, we have used a forward genetics approach to positionally identify polymorphic nucleotides controlling T cell-dependent inflammatory diseases using congenic mouse strains. Here, we identify the vitamin D3 receptor (Vdr) as a driver of inflammation. Congenic mice carrying a polymorphic Vdr allele overexpressed the receptor selectively in activated T cells, thereby escaping systemic calcaemic side effects that often constitute a confounding factor in the study of immunomodulation by vitamin D3. Mice overexpressing Vdr in T cells developed more severe collagen-induced arthritis (CIA) and exhibited an enhanced antigen-specific CD4+ T cell response. Deficiency of vitamin D3 completely protected mice from CIA by limiting the activation of antigen-specific T cell responses, and arthritis susceptibility was restored by re-administration of vitamin D3. We demonstrate that vitamin D3 signalling specifically through Vdr predominantly acts to enhance T cell proliferation, thereby contributing to inflammation. In conclusion, our results demonstrate that genetically determined expression of VDR codetermines the pro-inflammatory behaviour of activated T cells. Furthermore, our data suggest that the anti-inflammatory properties of vitamin D3 might be limited by high expression of VDR at the site of inflammation.
2020-09-28 | PXD019876 | Pride
Project description:Vitamin D deficiency is associated with a decline in muscle function and an increasing risk of muscle injury in athletes and the elderly. Nevertheless, how vitamin D3 and vitamin D receptor (VDR) regulate skeletal muscle cells under pro-fibrotic factor stimulation that could be pronounced during repetitive muscle damage have not been elucidated. Therefore, this study aimed to investigate the regulatory role of cholecalciferol (D3), calcidiol (25D3), calcitriol (1,25D3), and the effect of Vdr gene suppression under TGF-β1 stimulation in C2C12 mouse skeletal muscle cells. All forms of vitamin D3 exerted anti-fibrotic effects under TGF-β1 stimulation by suppression of COL1A1; however, D3 preserves this effect without a negative impact on myogenesis. Moreover, LC-MS/MS-based proteomics analysis revealed that myoblast fusion protein and mitochondrial regulation were altered following Vdr knockdown. These changes were associated with exacerbation of α-SMA expression in TGF-β1-treated cells and suggested VDR modulates fibrogenesis in skeletal muscle cells regardless of ligand binding. Under TGF-β1 stimulation, anti-fibrotic effects of 1,25D3 but not D3 were diminished after Vdr knockdown, supporting D3 action is not dependent on VDR activation. Collectively, understanding anti-fibrotic effects of vitamin D3 is beneficial for providing a strategy of vitamin D supplementation to counteract fibrosis development after muscle injury.
2025-12-01 | PXD062669 | Pride
Project description:Vitamin D deficiency and mutations in Vitamin D Receptor (VDR) are associated with liver disease and obesity, but the functions of vitamin D signaling in metabolism are poorly understood. Though vitamin D signaling is best known for its functions in mineral homeostasis and skeleton calcification in terrestrial vertebrates, this is unlikely to be the evolutionary function of vitamin D signaling. We utilize tissue-specific genetic modulation of Vdr signaling to investigate the function of the vitamin D endocrine system in zebrafish. We find that hepatocyte Vdr regulates organismal response to nutritional cues and coordinates hepatic and organismal energy metabolism by balancing energy storage and tissue growth.
2023-04-20 | GSE217120 | GEO
Project description:We investigated the genomic activity of vitamin D in primary prostate epithelial cells (PrE) through vitamin D receptor (VDR)-ChIP-sequencing. PrE cells treated with 50 nM 1,25D showed nuclear localization the VDR within 1 hr, persisting until 4 hr, and a 2 hr treatment was selected for ChIP-seq. Rigorous testing of the ChIP conditions and VDR antibody were performed. Nearly 5,000 VDR binding sites were identified.
2019-04-01 | GSE124576 | GEO
Project description:The active form of vitamin D, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), induces stable tolerogenesis in dendritic cells (DC). This process involves the Vitamin D receptor (VDR) which translocates to the nucleus, binds its cognate genomic sites and promotes epigenetic and transcriptional remodeling. In this study, we investigated the interplay between the vitamin D receptor (VDR) and transcription factors to induce DNA methylation changes, which might provide phenotypic stability to the tolerogenic phenotype of DCs.
2022-02-23 | GSE145584 | GEO
Project description:In the present study, we aimed to define the role of VDR in the overall lipid metabolism by transcriptomic and metabolomic analyses of human hepatocytes upon VDR activation by vitamin D (VitD) In this dataset we include the expression data obtained from HepG2 cells transfected with an insertless adenoviral vector or with an adenovirus encoding human VDR. Cells expressing VDR were treated with VitD or vehicle.
2020-04-01 | GSE138376 | GEO
Project description:Vitamin D induces anti-proliferative and differentiating effects in prostate cancer. Thus calcitriol, the hormonally active form of Vitamin D, and its analogs have been extensively studied in prostate cancer cells. Yet despite its importance, relatively little is known about the genome-scale mechanisms by which Vitamin D, through its cognate nuclear vitamin D receptor (VDR), exerts its regulatory functions at the genomic level. In this study, we defined VDR transcriptional networks in the LNCaP prostate cancer cell line by mapping the genomic binding sites of VDR and by identifying differentially expressed genes upon calcitriol treatment. We found that VDR and androgen receptor (AR) antagonistically regulate a subset of cell cycle-related genes that are over-expressed in prostate cancer tumors. The expression balance of these genes is partially regulated through the competition dynamics between AR and VDR binding to shared cis-regulatory elements. On such shared elements, we found that FOXA1 mediates this competition by serving as a pioneering factor for both AR and VDR binding. We also found significant enrichment of AR-, VDR-, and AR/VDR overlapping binding sites in prostate cancer-associated single-nucleotide polymorphism (SNP) intervals identified from genome-wide association studies (GWAS), providing genetic evidence to link AR, VDR and their crosstalk to prostate cancer susceptibilities. In particular, we found that in a cis-regulatory element of the RFX6 gene implicated in prostate cancer progression, an allelic variant increases prostate cancer risk by switching the antagonism between AR and VDR into a synergistic interaction. Examination of AR, VDR, and FOXA1 binding in LNCaP cells, in biological replicates
2015-08-01 | E-GEOD-64656 | biostudies-arrayexpress
Project description:Mutations of the lamin A/C gene (LMNA) cause a variety of diseases including dilated cardiomyopathy (DCM). LMNA-related DCM often leads to severe heart failure, but the underlying pathophysiology is unknown. Here we show that vitamin D receptor (VDR) signaling is critically involved in LMNA-related DCM. We established iPS cells from DCM patients with an LMNA mutation and found that the iPS cell-derived cardiomyocytes (iPSCMs) showed remarkable DNA damage and reduced contractility compared with the isogenic control. Screening of a chemical library revealed that vitamin D2 reduced DNA damage of the mutant iPSCMs. RNA sequencing analysis showed that expression levels of putative downstream genes of VDR including DNA repair factors were downregulated in the mutant iPSCMs, which were upregulated by vitamin D2. Protein-protein interaction screening revealed that the binding of VDR to mutant LMNA was more robust than to wild-type LMNA, resulting in attenuated VDR signaling in the mutant iPSCMs. Vitamin D2 administration reduced DNA damage and improved cardiac function in pressure overload-induced heart failure mice. These results indicate that impaired DNA repair caused by reduced transcriptional activity of VDR induces cardiac dysfunction of LMNA-related DCM and suggest that VDR signaling is a potential therapeutic target for patients with DCM and heart failure.
2025-03-01 | GSE182219 | GEO