Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Transcription profiling of human muscle tissue in patients with inflammatory myopathies

ABSTRACT: Molecular profiles of muscle tissue in patients with inflammatory myopathies

ORGANISM(S): Homo sapiens

SUBMITTER: Steven Alan Greenberg

PROVIDER: E-GEOD-281 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Molecular profiles of inflammatory myopathies.

Greenberg S A SA Sanoudou D D Haslett J N JN Kohane I S IS Kunkel L M LM Beggs A H AH Amato A A AA

Neurology 20021001 8

<h4>Objective</h4>To describe the use of large-scale gene expression profiles to distinguish broad categories of myopathy and subtypes of inflammatory myopathies (IM) and to provide insight into the pathogenesis of inclusion body myositis (IBM), polymyositis, and dermatomyositis.<h4>Methods</h4>Using Affymetrix GeneChip microarrays, the authors measured the simultaneous expression of approximately 10,000 genes in muscle specimens from 45 patients in four major disease categories (dystrophy, cong ...[more]

PMID: 12391344

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Project description:Objective: In idiopathic inflammatory myopathies (IIM) infiltration of immune cells into muscle and upregulation of MHC-I expression implies increased antigen presentation and involvement of the proteasome system. To decipher the role of immunoproteasomes in myositis, we investigated individual cell types and muscle tissues and focused on possible immune triggers. Methods: Expression of constitutive (PSMB5, -6, -7) and corresponding immunoproteasomal subunits (PSMB8, -9, -10) was analyzed by real-time RT-PCR in muscle biopsies and sorted peripheral blood cells of patients with IIM, non-inflammatory myopathies (NIM) and healthy donors (HD). Protein analysis in muscle biopsies was performed by western blot. Affymetrix HG-U133 platform derived transcriptome data from biopsies of different muscle diseases and from immune cell types as well as monocyte stimulation experiments were used for validation, coregulation and coexpression analyses. Results: Real-time RT-PCR revealed significantly increased expression of immunoproteasomal subunits (PSMB8/-9/-10) in DC, monocytes and CD8+ T-cells in IIM. In muscle biopsies, the immunosubunits were elevated in IIM compared to NIM and exceeded levels of matched blood samples. Proteins of PSMB8 and -9 were found only in IIM but not NIM muscle biopsies. Reanalysis of 78 myositis and 20 healthy muscle transcriptomes confirmed these results and revealed involvement of the antigen processing and presentation pathway. Comparison with reference profiles of sorted immune cells and healthy muscle confirmed upregulation of PSMB8 and -9 in myositis biopsies beyond infiltration related changes. This upregulation correlated highest with STAT1, IRF1 and IFNM-NM-3 expression. Elevation of T-cell specific transcripts in active IIM muscles was accompanied by increased expression of DC and monocyte marker genes and thus reflects the cell type specific involvement observed in peripheral blood. Conclusions: Immunoproteasomes seem to indicate IIM activity and suggest that dominant involvement of antigen processing and presentation may qualify these diseases exemplarily for the evolving therapeutic concepts of immunoproteasome specific inhibition. Investigation of constitutive and immunoproteasomal subunit expression in muscle tissue of patients with inflammatory and non-inflammatory myopathies These transcriptomes were used as reference signatures of different immune cell types in order to estimate the contribution of immune cell transcripts to the muscle transcriptomes investigated in the datasets GSE2044, GSE3112, GSE5370, GSE39454, GSE3307, GSE13205, GSE10685.

Dataset Information

Transcription profiling of human muscle tissue in patients with inflammatory myopathies

Publications

Molecular profiles of inflammatory myopathies.

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