Circulating plasma microRNA profiling in patients with polymyositis/dermatomyositis before and after treatment
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE94535 | GEO | 2017/02/07
SECONDARY ACCESSION(S): PRJNA371425
REPOSITORIES: GEO
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Project description:Dermatomyositis and polymyositis (DM/PM) are systemic autoimmune diseases characterized by proximal muscle weakness. The underlying pathogenetic mechanism of this disease remains elusive. Here, using proteomics analysis, a great overlap of differentially expressed plasma exosomal proteins involved in the complement and coagulation cascades pathway, including FGA, FGB, FGG, C1QB, C1QC and VWF, were identified in DM/PM patients versus HCs. Correlation analysis revealed that the expression levels of complement-associated proteins (C1QB and C1QC) correlated positively with CRP, ESR and platelet count. ROC curve analysis demonstrated that complement and coagulation cascade-associated proteins could be strong predictors for DM/PM. Additionally, we also identified several other proteins that were differentially expressed in DM and PM, respectively. And the selected candidate proteins were further validated by PRM. Together, these exosome-derived proteins might participate in microvascular damage in DM/PM through the activation of the complement and coagulation cascades pathway and function as biomarkers for the clinical diagnosis of DM/PM.
2023-03-11 | PXD037608 | Pride
Project description:Dermatomyositis and polymyositis (DM/PM) are systemic autoimmune diseases characterized by proximal muscle weakness. The underlying pathogenetic mechanism of this disease remains elusive. Here, using proteomics analysis, a great overlap of differentially expressed plasma exosomal proteins involved in the complement and coagulation cascades pathway, including FGA, FGB, FGG, C1QB, C1QC and VWF, were identified in DM/PM patients versus HCs. Correlation analysis revealed that the expression levels of complement-associated proteins (C1QB and C1QC) correlated positively with CRP, ESR and platelet count. ROC curve analysis demonstrated that complement and coagulation cascade-associated proteins could be strong predictors for DM/PM. Additionally, we also identified several other proteins that were differentially expressed in DM and PM, respectively. And the selected candidate proteins were further validated by PRM. Together, these exosome-derived proteins might participate in microvascular damage in DM/PM through the activation of the complement and coagulation cascades pathway and function as biomarkers for the clinical diagnosis of DM/PM.
2023-03-11 | PXD037483 | Pride
Project description:Expression profiling of human myositis muscle samples This study was designed to compare expression signatures among the various types of inflammatory myopathy, dermatomyositis (DM), inclusion body myositis (IBM), necrotizing myopathy (NM), nonspecific myopathy (NS), and polymyositis (PM) compared to normal (NL) muscle.
2019-08-30 | GSE128470 | GEO
Project description:Muscle biopsies were taken from 6 patients with dermatomyositis, 4 with polymyositis and 5 not myopathic subjects as controls. The genome-wide expression patterns were compared using Affymetrix HG-U133A chips. Experiment Overall Design: Gene expression profiles were generated for 15 individuals.
2011-04-23 | E-MEXP-2681 | biostudies-arrayexpress
Project description:Dermatomyositis is a cutaneous and muscular auto-immune condition associated with specific autoantibodies. MDA5 antibody-associated DM has higher mortality. We demonstrate here for the first time using skin microarray analysis that MDA5+ DM is associated with a greater type I interferon skin signature than MDA5- DM, mainly involving the IFN- κ member produced by skin keratinocytes
2019-10-27 | GSE128314 | GEO
Project description:Dermatomyositis (DM) is an idiopathic inflammatory myopathy characterized by cutaneous manifestations. We first identified the profiles of noncoding RNAs (lncRNAs and miRNAs) in peripheral neutrophil exosomes (EXOs) of DM patients and explored their potential functional roles. Bioinformatics analyses were performed with R packages. Real-time quantitative PCR was used to validate the altered RNAs in DM neutrophil EXO-stimulated human dermal microvascular endothelial cells (HDMECs) and human skeletal muscle myoblasts (HSkMCs). In DM neutrophil EXOs, 124 upregulated lncRNAs (with 1,392 target genes), 255 downregulated lncRNAs (with 1867 target genes), 17 upregulated miRNAs (with 2,908 target genes), and 15 downregulated miRNAs (with 2,176 target genes) were identified. GO analysis showed that the differentially expressed (DE) lncRNAs and DE miRNAs participated in interleukin-6 and interferon-beta production, skeletal muscle cell proliferation and development, and endothelial cell development and differentiation. KEGG analysis suggested that DE lncRNAs and DE miRNAs were enriched in the PI3K–Akt, MAPK, AMPK and FoxO signalling pathways. Many novel and valuable DE lncRNAs and DE miRNAs interacted and cotargeted in the PI3K–Akt, MAPK, AMPK and FoxO signalling pathways. Our study suggests that neutrophil EXOs participate in DM pathogenesis through lncRNAs and miRNAs in the PI3K–Akt, MAPK, AMPK and FoxO signalling pathways.
2021-09-17 | GSE155281 | GEO
Project description:Objectives: The idiopathic inflammatory myopathies (IIMs) are heterogeneous autoimmune conditions of skeletal muscle inflammation and weakness. MicroRNAs (miRNAs) are short, non-coding RNA which regulate gene expression of target mRNAs. The aim of this study was to profile miRNA and mRNA in IIM and identify miRNA-mRNA relationships which may be relevant to disease. Materials and methods: mRNA and miRNA in whole blood samples from 7 polymyositis (PM), 7 dermatomyositis (DM), 5 inclusion body myositis (IBM) and 5 non-myositis controls was profiled using next generation RNA sequencing. Gene ontology and pathway analyses were performed using GOseq and Ingenuity Pathway Analysis. Dysregulation of miRNAs and opposite dysregulation of predicted target mRNAs in IIM subgroups was validated using RTqPCR and investigated by transfecting human skeletal muscle cells with miRNA mimic. Results Analysis of differentially expressed genes showed that interferon signalling and anti-viral response pathways were upregulated in PM and DM compared to controls. An anti-Jo1 autoantibody positive subset of PM and DM (n=5) had more significant upregulation and predicted activation of interferon signalling and highlighted T-helper (Th1 and Th2) cell pathways. In miRNA profiling miR-96-5p was significantly upregulated in PM, DM and the anti-Jo1positive subset. RTqPCR replicated miR-96-5p upregulation and predicted mRNA target (ADK, CD28 and SLC4A10) downregulation. Transfection of a human skeletal muscle cell line with miR-96-5p mimic resulted in significant downregulation of ADK. Conclusion: MiRNA and mRNA profiling identified dysregulation of interferon signalling, anti-viral response and T-helper cell pathways, and indicates a possible role for miR-96-5p regulation of ADK in pathogenesis of IIM.
2019-07-31 | GSE125977 | GEO
Project description:MHC-I overexpression in muscle biopsies is a hallmark of inflammatory myopathies.However the mechanisms of MHC-I overexpression in each disease is not well understood. Microarray analysis from MHC-I-microdissected myofibers showed a differential expression signature in each inflammatory myopathy. Innate immunity and IFN-I pathways are upregulated vs healthy controls, specifically in dermatomyositis (DM). RNA from MHC-I-positive myofibers were obtained from muscle biopsies of 5 patients with dermatomyositis, 5 with polymyositis, 4 with inclusion body myositis and normal looking fibers from healthy controls.
2013-12-01 | E-GEOD-48280 | biostudies-arrayexpress
Project description:muscle biopsies of normal and dermatomyositis patients Keywords: other
2004-10-01 | GSE1551 | GEO
Project description:Inclusion body myositis (IBM) is an autoimmune and degenerative disorder of skeletal muscle. The B cell infiltrates in IBM muscle tissue are predominantly fully differentiated antibody-secreting plasma cells, with scarce naïve or memory B cells. The role of this infiltrate in the disease pathology is not well understood. To better define the humoral response in IBM, we used adaptive immune receptor repertoire sequencing to generate large B cell receptor (BCR) repertoire libraries from IBM muscle biopsies and compared them to those generated from dermatomyositis (DM), polymyositis (PM), and circulating CD27+ memory B cells, derived from healthy controls and antibody secreting cells (ASC) collected following vaccination. The repertoire properties of the IBM infiltrate included: expanded clones that equaled or exceeded the highly clonal vaccine-associated ASC repertoire; reduced somatic mutation selection pressure in the complementary determining regions and framework regions; and enriched usage of class switched IgG and IgA isotypes, with a minor population of IgM expressing cells. These IBM IgM-expressing population revealed unique features, including an elevated somatic mutation frequency and distinct CDR3 physicochemical properties., These findings demonstrate that the IBM muscle BCR repertoire is highly distinct from DM and PM and circulating antigen-experienced subsets, suggesting that it may form through selection by a disease-specific set of antigens.
2023-04-25 | GSE227124 | GEO