Vitamin D promotes tissue repair and host defense responses against microbial infection in airway organoids
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE224094 | GEO | 2023/07/12
REPOSITORIES: GEO
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Project description:To study the pleiotropic effects of vitamin D in airway host defense, we use airway epithelial organoids cultured on air-liquid interface (ALI), originating from three chronic rhinosinusitis patients, marking as N66, N67 and N69, respectively. 24 hours prior to infection of Staphylococcus Aureus or influenza virus H1N1, 10nM and 100nM 1,25(OH)2D3 were added respectively to the medium in the lower chamber of Transwells with organoids. 24 hours post infection, 100μl DPBS were added to the apical surface of organoids for 20 minutes and then cellular secretion diluted in the DPBS were collected for proteomics analysis. The control groups without 1,25(OH)2D3 treatment were denoted as ND and those without infection were denoted as C. We applied a mass spectrometry-based tandem mass tag quantitative proteomics to analyze the cellular secretion from airway epithelial organoids, so as to study the host defense effects of vitamin D against pathogen infection.
2022-02-28 | PXD031956 | iProX
Project description:Three independent repeats of ChIP-seq or ChIPmentation with THP-1 cells after treatment with either 1,25(OH)2D3 (VD) or control (EtOH) using antibody against CEBPA (3 time points).
2018-12-18 | GSE124032 | GEO
Project description:To profile the changes in the pattern of gene expression in human OCa cells induced by 1,25(OH)2D3, OVCAR3 cells were treated with 0.1 pM 1,25(OH)2D3 for 0, 8, 24 and 72 h. The cells were harvested, RNA was extracted, and Affmetrix microarrays were hybridized. OVCAR3 cells were treated with 0.1 pM 1,25(OH)2D3 for 0, 8, 24 and 72 hours. 1,25(OH)2D3 was added at different times to allow the treated cells to be harvested at the same time. Ethanol was included as vehicle controls and all cells were exposed to the same amount of ethanol for the same length of time. Total RNA was extracted using Trizol reagent (Invitrogen) and purified using Qiagen Rneasy kit as recommended by Affymetrix. In the initial set of array analysis with U95 chips, GADD45 was identified to be a VD-induced gene in OVCAR3 cells, which was confirmed by a follow-up study to be a primary target gene. For the array analyses with U133A chips, the response to 1,25(OH)2D3 of the cells used for RNA isolation was ensured by Northern blotting analysis of GADD45. Three independent experiments were performed.
2011-01-28 | E-GEOD-26903 | biostudies-arrayexpress
Project description:Heterogeneous nuclear ribonucleoprotein (hnRNP) C1/C2 plays a pivotal role in vitamin D receptor (VDR) signaling by acting as a vitamin D response element (VDRE)-binding protein (VDRE-BP). Transcriptional regulation by active 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) involves occupancy of VDRE by VDRE-BP or 1,25(OH)2D3 bound-VDR. This relationship is disrupted by over-expression of VDRE-BP and can cause a form of human hereditary vitamin D-resistant rickets (HVDRR). DNA array analyses using B-cells from an HVDRR patient and matched control defined a sub-cluster of genes where 1,25(OH)2D3-regulated transcription was abrogated by over-expression of VDRE-BP. Amongst these, the DNA-damage-inducible transcript 4 (DDIT4), an inhibitor of mammalian target of rapamycin (mTOR) signaling, was also induced by 1,25(OH)2D3 in human osteoblasts. Chromatin immunoprecipitation using 1,25(OH)2D3-treated osteoblasts confirmed that liganded VDR and VDRE-BP compete for binding to the proximal promoter of the DDIT4 gene in a similar fashion to other known 1,25(OH)2D3-target genes. Treatment of osteoblasts with 1,25(OH)2D3 induced DDIT4 expression and suppressed phosphorylated S6K1T389 protein (a downstream target of mTOR). The functional importance of this for 1,25(OH)2D3 responses in osteoblasts was underlined by the fact that siRNA knockdown of DDIT4 expression suppressed antiproliferative and cell growth responses to 1,25(OH)2D3. These data confirm that VDRE-BP is required for normal 1,25(OH)2D3-mediated transcription and cell function in osteoblasts. Conversely over-expression of VDRE-BP exerts a dominant-negative effect on transcription of 1,25(OH)2D3-target genes. Characterization of VDRE-BP action in 1,25(OH)2D3-treated osteoblasts highlights an entirely novel role for vitamin D as a regulator of mTOR – a known ‘master regulator’ of cell function.
2010-11-19 | GSE22523 | GEO
Project description:Dietary supplementation of vitamin D is commonly recommended to patients with multiple sclerosis (MS). We investigated the effect of 1,25-dihydroxyvitamin-D3 (1,25-(OH)2D3) on the brain proteome in the cuprizone model during remyelination. Mice were demyelinated with dietary cuprizone for 7 weeks. The mice received intra-peritoneal injections of 1,25-(OH)2D3 or placebo twice a week, from week 6 and throughout week 10. Brain samples were taken after 7 weeks (demyelinated), after 8 weeks (1 week remyelination) and after 10 weeks (3 weeks of remyelination). The six experimental groups were labeled with TMT, mixed mode HPLC fractionation, and applied to LC-MS which enabled quantification of 5062 proteins with high confidence.
2017-08-16 | PXD002347 | Pride
Project description:Heterogeneous nuclear ribonucleoprotein (hnRNP) C1/C2 plays a pivotal role in vitamin D receptor (VDR) signaling by acting as a vitamin D response element (VDRE)-binding protein (VDRE-BP). Transcriptional regulation by active 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) involves occupancy of VDRE by VDRE-BP or 1,25(OH)2D3 bound-VDR. This relationship is disrupted by over-expression of VDRE-BP and can cause a form of human hereditary vitamin D-resistant rickets (HVDRR). DNA array analyses using B-cells from an HVDRR patient and matched control defined a sub-cluster of genes where 1,25(OH)2D3-regulated transcription was abrogated by over-expression of VDRE-BP. Amongst these, the DNA-damage-inducible transcript 4 (DDIT4), an inhibitor of mammalian target of rapamycin (mTOR) signaling, was also induced by 1,25(OH)2D3 in human osteoblasts. Chromatin immunoprecipitation using 1,25(OH)2D3-treated osteoblasts confirmed that liganded VDR and VDRE-BP compete for binding to the proximal promoter of the DDIT4 gene in a similar fashion to other known 1,25(OH)2D3-target genes. Treatment of osteoblasts with 1,25(OH)2D3 induced DDIT4 expression and suppressed phosphorylated S6K1T389 protein (a downstream target of mTOR). The functional importance of this for 1,25(OH)2D3 responses in osteoblasts was underlined by the fact that siRNA knockdown of DDIT4 expression suppressed antiproliferative and cell growth responses to 1,25(OH)2D3. These data confirm that VDRE-BP is required for normal 1,25(OH)2D3-mediated transcription and cell function in osteoblasts. Conversely over-expression of VDRE-BP exerts a dominant-negative effect on transcription of 1,25(OH)2D3-target genes. Characterization of VDRE-BP action in 1,25(OH)2D3-treated osteoblasts highlights an entirely novel role for vitamin D as a regulator of mTOR – a known ‘master regulator’ of cell function. We performed gene expression microarray analysis in HVDRR EBV-transformed B-cells and control cells in the presence or absence of vitamin D.
2010-11-19 | E-GEOD-22523 | biostudies-arrayexpress
Project description:The Wnt/b-catenin signalling pathway is essential for intestinal epithelium homeostasis, but its aberrant activation is a hallmark of colorectal cancer (CRC). Several studies indicate that the bioactive vitamin D metabolite 1a,25-dihydroxyvitamin D3 (1,25(OH)2D3) inhibits proliferation and promotes epithelial differentiation of colon carcinoma cells in part through antagonism of the Wnt/b-catenin pathway. It is now accepted that stromal fibroblasts are crucial in healthy and pathologic intestine: pericryptal myofibroblasts are constituents of the stem cell niche and cancer-associated fibroblasts (CAFs) contribute to CRC progression. However, studies on the combined action of 1,25(OH)2D3 and Wnt factors in colon fibroblasts are lacking. Here we show by global transcriptomic studies that 1,25(OH)2D3 and Wnt3A have profound, additive, partially overlapping effects on the gene expression profile of CCD-18Co human colon myofibroblasts. Moreover, 1,25(OH)2D3 and Wnt3A inhibit CCD-18Co cell proliferation and migration, while 1,25(OH)2D3 reduces, but Wnt3A increases, their capacity to contract collagen gels (a marker of fibroblast activation). These data were largely confirmed in patient-derived primary colon normal fibroblasts and CAFs, and in fibroblasts from other origins. Our results indicate that 1,25(OH)2D3 and Wnt3A are strong regulators of colon fibroblast biology and contribute to a better knowledge of intestinal homeostasis and stromal fibroblast action in CRC.
2019-05-30 | GSE120106 | GEO
Project description:Vitamin D deficiency is associated with high risk of colon cancer and a variety of other diseases. The active vitamin D metabolite 1alpha,25-dihydroxyvitamin D3 (1,25(OH)2D3) regulates gene transcription via its nuclear receptor (VDR), and posttranscriptional regulatory mechanisms of gene expression have also been proposed. We have identified microRNA-22 (miR-22) and several other miRNA species as 1,25(OH)2D3 targets in human colon cancer cells. Remarkably, miR-22 is induced by 1,25(OH)2D3 in a time-, dose-, and VDR-dependent manner. In SW480-ADH and HCT116 cells, miR-22 loss-of-function by transfection of a miR-22 inhibitor (anti-miR-22) suppresses the effect of 1,25(OH)2D3. Additionally, miR-22 inhibition increases cell migration per se and decreases the antimigratory effect of 1,25(OH)2D3 in both cell types. In silico analysis shows a significant overlap between genes suppressed by 1,25(OH)2D3 and miR-22 putative target genes. Consistently, miR-22 inhibition abrogates the reduction by 1,25(OH)2D3–mediated suppression of NELL2, OGN, HNRPH1, and NFAT5 genes. In 39 out of 50 (78%) human colon cancer patients, miR-22 expression was found lower in the tumor than in the matched normal tissue and correlated directly with that of VDR. Our results indicate that miR-22 is induced by 1,25(OH)2D3 in human colon cancer cells and it may contribute to its antitumor action against this neoplasia.
2011-12-20 | GSE34564 | GEO
Project description:Vitamin D deficiency is associated with high risk of colon cancer and a variety of other diseases. The active vitamin D metabolite 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) regulates gene transcription via its nuclear receptor (VDR), and posttranscriptional regulatory mechanisms of gene expression have also been proposed. We have identified microRNA-22 (miR-22) and several other miRNA species as 1,25(OH)2D3 targets in human colon cancer cells. Remarkably, miR-22 is induced by 1,25(OH)2D3 in a time-, dose-, and VDR-dependent manner. In SW480-ADH and HCT116 cells, miR-22 loss-of-function by transfection of a miR-22 inhibitor (anti-miR-22) suppresses the effect of 1,25(OH)2D3. Additionally, miR-22 inhibition increases cell migration per se and decreases the antimigratory effect of 1,25(OH)2D3 in both cell types. In silico analysis shows a significant overlap between genes suppressed by 1,25(OH)2D3 and miR-22 putative target genes. Consistently, miR-22 inhibition abrogates the reduction by 1,25(OH)2D3–mediated suppression of NELL2, OGN, HNRPH1, and NFAT5 genes. In 39 out of 50 (78%) human colon cancer patients, miR-22 expression was found lower in the tumor than in the matched normal tissue and correlated directly with that of VDR. Our results indicate that miR-22 is induced by 1,25(OH)2D3 in human colon cancer cells and it may contribute to its antitumor action against this neoplasia. We have analysed a human colon cancer cell line, SW480-ADH, treated with 1,25(OH)2D3 or isopropanol (vehicle) at three different time points (24, 48 and 96 hours). Each experiment was replicated 2 times by dye swap.
2011-12-20 | E-GEOD-34564 | biostudies-arrayexpress
Project description:ChIP-seq for the insulator protein CTCF in THP-1 cells after stimulation with the the natural VDR ligand 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) THP-1 cells were treated for 24 h with 100 nM 1,25(OH)2D3 before ChIP assay
2016-07-04 | E-GEOD-69962 | biostudies-arrayexpress