Unraveling Natalizumab Effects on Deregulated miR-17 Expression in CD4+ T Cells of Patients with Relapsing-Remitting Multiple Sclerosis
Autor: | Maria Meira, Ludwig Kappos, Tobias Derfuss, Claudia Sievers, Maria Rasenack, Francine Hoffmann, Jens Kuhle, Raija L.P. Lindberg |
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Jazyk: | angličtina |
Rok vydání: | 2014 |
Předmět: |
CD4-Positive T-Lymphocytes
Male Lymphocyte Activation Natalizumab Cell Movement Immunology and Allergy Regulation of gene expression Bcl-2-Like Protein 11 Cell Cycle General Medicine Middle Aged Cell cycle medicine.anatomical_structure Female Signal Transduction Research Article medicine.drug Adult Cyclin-Dependent Kinase Inhibitor p21 lcsh:Immunologic diseases. Allergy Article Subject T cell Immunology Protein Serine-Threonine Kinases Biology Antibodies Monoclonal Humanized Multiple Sclerosis Relapsing-Remitting Downregulation and upregulation Proto-Oncogene Proteins microRNA medicine Humans PTEN Cell Proliferation Multiple sclerosis PTEN Phosphohydrolase Receptor Transforming Growth Factor-beta Type II Membrane Proteins medicine.disease MicroRNAs Gene Expression Regulation Case-Control Studies Cell Migration Inhibition Cancer research biology.protein Apoptosis Regulatory Proteins lcsh:RC581-607 Receptors Transforming Growth Factor beta E2F1 Transcription Factor |
Zdroj: | Journal of Immunology Research, Vol 2014 (2014) Journal of Immunology Research |
ISSN: | 2314-8861 |
DOI: | 10.1155/2014/897249 |
Popis: | MicroRNAs (miRNAs) are a family of noncoding RNAs that play critical roles in the posttranscriptional regulation of gene expression. Accumulating evidence supports their involvement in the pathogenesis of multiple sclerosis (MS). Here, we compare miR-17 expressions in CD4+T cells from relapsing-remitting (RR) MS patients treated with natalizumab versus untreated patients. miR-17 was downregulated under natalizumab treatment and upregulated during relapse, therefore supporting a possible role of miR-17 in MS immunopathogenesis. Downregulation of miR-17 was associated with upregulation of PTEN, BIM, E2F1, and p21 target genes.In vitromiR-17 inhibition was associated with upregulation of the same targets and resulted in impaired CD4+T cell activation and proliferation. We further describe deregulated TGFBR2 expression in untreated patients versus healthy volunteers (HVs) and confirmin vitrothe link between miR-17 and TGFBR2 expressions. These findings support an effect of natalizumab on expression of specific miRNA and subsequent expression of genes involved in proliferation and control of the cell cycle. |
Databáze: | OpenAIRE |
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