Stromal transcriptional profiles reveal hierarchies of anatomical site, serum response and disease and identify disease specific pathways
| Autor: | Philipp Antczak, Karim Raza, Andrew Filer, Greg Parsonage, Andrew M. C. Thomas, Dagmar Scheel-Toellner, Mark J. Pearson, Holly M. Legault, Christopher D. Buckley, Margot O'Toole, Francesco Falciani |
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| Rok vydání: | 2014 |
| Předmět: |
Pathology
medicine.medical_specialty Stromal cell Databases Factual Inflammatory arthritis Science Arthritis Bone Marrow Cells Biology Extracellular matrix Arthritis Rheumatoid Somatomedins Osteoarthritis medicine Humans Fibroblast Cells Cultured Oligonucleotide Array Sequence Analysis Skin Principal Component Analysis Multidisciplinary Synovial Membrane Integrin beta3 Fibroblasts medicine.disease Actin cytoskeleton 3. Good health Actin Cytoskeleton medicine.anatomical_structure Medicine Synovial membrane Wound healing Transcriptome Signal Transduction Research Article |
| Zdroj: | PLoS ONE PLoS ONE, Vol 10, Iss 3, p e0120917 (2015) |
| ISSN: | 1932-6203 |
| Popis: | Synovial fibroblasts in persistent inflammatory arthritis have been suggested to have parallels with cancer growth and wound healing, both of which involve a stereotypical serum response programme. We tested the hypothesis that a serum response programme can be used to classify diseased tissues, and investigated the serum response programme in fibroblasts from multiple anatomical sites and two diseases. To test our hypothesis we utilized a bioinformatics approach to explore a publicly available microarray dataset including rheumatoid arthritis (RA), osteoarthritis (OA) and normal synovial tissue, then extended those findings in a new microarray dataset representing matched synovial, bone marrow and skin fibroblasts cultured from RA and OA patients undergoing arthroplasty. The classical fibroblast serum response programme discretely classified RA, OA and normal synovial tissues. Analysis of low and high serum treated fibroblast microarray data revealed a hierarchy of control, with anatomical site the most powerful classifier followed by response to serum and then disease. In contrast to skin and bone marrow fibroblasts, exposure of synovial fibroblasts to serum led to convergence of RA and OA expression profiles. Pathway analysis revealed three inter-linked gene networks characterising OA synovial fibroblasts: Cell remodelling through insulin-like growth factors, differentiation and angiogenesis through -3 integrin, and regulation of apoptosis through CD44. We have demonstrated that Fibroblast serum response signatures define disease at the tissue level, and that an OA specific, serum dependent repression of genes involved in cell adhesion, extracellular matrix remodelling and apoptosis is a critical discriminator between cultured OA and RA synovial fibroblasts. |
| Databáze: | OpenAIRE |
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