{"database":"biostudies-arrayexpress","file_versions":[],"scores":null,"additional":{"submitter":["Celine Berthier"],"organism":["Homo sapiens"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/E-GEOD-26951"],"description":["Systemic lupus erythematosus (SLE) is characterized by increased vascular risk due to premature atherosclerosis independent of traditional risk factors. We previously proposed that interferon-α plays a crucial role in premature vascular damage in SLE. IFN-α alters the balance between endothelial cell apoptosis and vascular repair mediated by endothelial progenitor cells (EPCs) and myeloid circulating angiogenic cells (CACs). Here we demonstrate that IFN-α promotes an antiangiogenic signature in SLE and control EPCs/CACs, characterized by transcriptional repression of IL-1α and β, IL-1 receptor 1 and vascular endothelial growth factor A (VEGF-A) and upregulation of IL-1 receptor antagonist (IL-1RN) and the decoy receptor IL1-R2. IL-1β promotes significant improvement in the functional capacity of lupus EPCs/CACs, therefore abrogating the deleterious effects of IFN-α. We used microarrays to analyze the effect of IFNα on peripheral blood EPCs/CACs and on bone marrow EPCs exposed to proangiogenic stimulation. Human healthy EPCs from bone marrow were isolated and cultured under proangiogenic stimulation; after IFNa incubation or not, RNA was extracted and processed for hybridization on Affymetrix microarrays."],"repository":["biostudies-arrayexpress"],"sample_protocol":["Labeling - Biotinylated cRNA were prepared according to the standard Affymetrix protocol from total RNA (Expression Analysis Technical Manual, Affymetrix).","Hybridization - Standard Affymetrix protocol (GeneChip Expression Analysis Technical Manual).","Nucleic Acid Extraction - Total RNA was isolated with Tri-pure (Roche), and further purified and concentrated using an Rneasy kit (Qiagen).","Sample Processing - Cells were incubated in the presence or absence of IFNa for 6 hours prior to RNA harvesting."],"figure_sub":["MIAME Score","Raw Data","Organization","Assays and Data","Processed Data","Additional Files","MAGE-TAB Files","Array Designs"],"data_protocol":["Feature Extraction - The data were analyzed using the GenePattern pipeline: the RMA method and Human Entrez Gene custom CDF annotation version 10 was used for the normalization. Healthy EPCs, lupus EPCs and healthy bone marrow EPCs were normalized separately.","Image Adquisition - GeneChips were scanned using the Affymetrix 3000 7G GeneChip Scanner with Autoloader.","Assay Data Transformation - ID_REF = <br>VALUE = Log base 2 normalized expression value"],"omics_type":["Unknown","Transcriptomics","Genomics","Proteomics"],"pubmed_abstract":["Systemic lupus erythematosus (SLE) is characterized by increased vascular risk due to premature atherosclerosis independent of traditional risk factors. We previously proposed that IFN-α plays a crucial role in premature vascular damage in SLE. IFN-α alters the balance between endothelial cell apoptosis and vascular repair mediated by endothelial progenitor cells (EPCs) and myeloid circulating angiogenic cells (CACs). In this study, we demonstrate that IFN-α promotes an antiangiogenic signature in SLE and control EPCs/CACs, characterized by transcriptional repression of IL-1α and β, IL-1R1, and vascular endothelial growth factor A, and upregulation of IL-1R antagonist and the decoy receptor IL-1R2. IL-1β promotes significant improvement in the functional capacity of lupus EPCs/CACs, therefore abrogating the deleterious effects of IFN-α. The beneficial effects from IL-1 are mediated, at least in part, by increases in EPC/CAC proliferation, by decreases in EPC/CAC apoptosis, and by preventing the skewing of CACs toward nonangiogenic pathways. IFN-α induces STAT2 and 6 phosphorylation in EPCs/CACs, and JAK inhibition abrogates the transcriptional antiangiogenic changes induced by IFN-α in these cells. Immunohistochemistry of renal biopsies from patients with lupus nephritis, but not anti-neutrophil cytoplasmic Ab-positive vasculitis, showed this pathway to be operational in vivo, with increased IL-1R antagonist, downregulation of vascular endothelial growth factor A, and glomerular and blood vessel decreased capillary density, compared with controls. Our study introduces a novel putative pathway by which type I IFNs may interfere with vascular repair in SLE through repression of IL-1-dependent pathways. This could promote atherosclerosis and loss of renal function in this disease."],"study_type":["transcription profiling by array"],"species":["Homo sapiens"],"pubmed_title":["The detrimental effects of IFN-α on vasculogenesis in lupus are mediated by repression of IL-1 pathways: potential role in atherogenesis and renal vascular rarefaction."],"pubmed_authors":["Celine Berthier","Thacker SG, Berthier CC, Mattinzoli D, Rastaldi MP, Kretzler M, Kaplan MJ","Matthias Kretzler","Mariana Kaplan","Maria Rastaldi","Deborah Mattinzoli","Seth Thacker"],"additional_accession":[]},"is_claimable":false,"name":"Expression data from human healthy CD133+ bone marrow EPCs","description":"Systemic lupus erythematosus (SLE) is characterized by increased vascular risk due to premature atherosclerosis independent of traditional risk factors. We previously proposed that interferon-α plays a crucial role in premature vascular damage in SLE. IFN-α alters the balance between endothelial cell apoptosis and vascular repair mediated by endothelial progenitor cells (EPCs) and myeloid circulating angiogenic cells (CACs). Here we demonstrate that IFN-α promotes an antiangiogenic signature in SLE and control EPCs/CACs, characterized by transcriptional repression of IL-1α and β, IL-1 receptor 1 and vascular endothelial growth factor A (VEGF-A) and upregulation of IL-1 receptor antagonist (IL-1RN) and the decoy receptor IL1-R2. IL-1β promotes significant improvement in the functional capacity of lupus EPCs/CACs, therefore abrogating the deleterious effects of IFN-α. We used microarrays to analyze the effect of IFNα on peripheral blood EPCs/CACs and on bone marrow EPCs exposed to proangiogenic stimulation. Human healthy EPCs from bone marrow were isolated and cultured under proangiogenic stimulation; after IFNa incubation or not, RNA was extracted and processed for hybridization on Affymetrix microarrays.","dates":{"release":"2011-04-13T00:00:00Z","modification":"2022-11-28T06:08:26.069Z","creation":"2022-01-28T18:17:19.288Z"},"accession":"E-GEOD-26951","cross_references":{"GEO":["GSE26951"],"pubmed":["20805419"],"EFO":["EFO_0002768"],"doi":["10.4049/jimmunol.1001782"]}}