Altered microRNA expression profile with miR-146a upregulation in CD4 + T cells from patients with rheumatoid arthritis
| Autor: | Jinjun Zhang, Liwei Lu, Jingyi Li, Jinyu Zhang, Qiuye Guo, Yongfei Fang, Xiaolan Fu, Liyun Zou, Yuzhang Wu, Jingbo Zhang, Ying Wan, Hongli Liu |
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| Jazyk: | angličtina |
| Rok vydání: | 2010 |
| Předmět: |
Adult
CD4-Positive T-Lymphocytes Male medicine.medical_treatment Immunology Arthritis Rheumatoid - metabolism - pathology Apoptosis MicroRNAs - metabolism Jurkat cells Transcriptome Arthritis Rheumatoid Adaptor Proteins Signal Transducing - metabolism Rheumatology microRNA Gene expression Synovial Fluid Immunology and Allergy Medicine Humans Up-Regulation - physiology CD4-Positive T-Lymphocytes - metabolism - pathology Adaptor Proteins Signal Transducing business.industry Tumor Necrosis Factor-alpha MicroRNA Expression Profile Middle Aged Up-Regulation MicroRNAs Cytokine Case-Control Studies Cancer research Linear Models Tumor necrosis factor alpha Female business Apoptosis Regulatory Proteins Biomarkers Research Article |
| Zdroj: | Arthritis Research & Therapy |
| Popis: | Introduction: Increasing evidence indicates that microRNAs (miRNAs) play a critical role in the pathogenesis of inflammatory diseases. The aim of the study was to investigate the expression pattern and function of miRNAs in CD4 + T cells from patients with rheumatoid arthritis (RA).Methods: The expression profile of miRNAs in CD4 + T cells from synovial fluid (SF) and peripheral blood of 33 RA patients was determined by microarray assay and validated by qRT-PCR analysis. The correlation between altered expression of miRNAs and cytokine levels was determined by linear regression analysis. The role of miR-146a overexpression in regulating T cell apoptosis was evaluated by flow cytometry. A genome-wide gene expression analysis was further performed to identify miR-146a-regulated genes in T cells.Results: miRNA expression profile analysis revealed that miR-146a expression was significantly upregulated while miR-363 and miR-498 were downregulated in CD4 + T cells of RA patients. The level of miR-146a expression was positively correlated with levels of tumor necrosis factor-alpha (TNF-α), and in vitro studies showed TNF-α upregulated miR-146a expression in T cells. Moreover, miR-146a overexpression was found to suppress Jurkat T cell apoptosis. Finally, transcriptome analysis of miR-146a overexpression in T cells identified Fas associated factor 1 (FAF1) as a miR-146a-regulated gene, which was critically involved in modulating T cell apoptosis.Conclusions: We have detected increased miR-146a in CD4 + T cells of RA patients and its close correlation with TNF-α levels. Our findings that miR-146a overexpression suppresses T cell apoptosis indicate a role of miR-146a in RA pathogenesis and provide potential novel therapeutic targets. © 2010 Li et al.; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. published_or_final_version |
| Databáze: | OpenAIRE |
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