| Altered expression of miR-203 in rheumatoid arthritis synovial fibroblasts and its role in fibroblast activation. | |
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MedLine Citation:
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PMID: 20981815 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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OBJECTIVE.: MicroRNAs are recognized as important regulators of a variety of fundamental biological processes. Previously, we described increased expression of miR-155 and miR-146a in rheumatoid arthritis (RA) and showed a repressive effect of miR-155 on MMP expression in RA synovial fibroblasts (RASFs). Now, we found altered expression of miR-203 in RASFs and analyzed its role in activation of fibroblasts. METHODS.: Differentially expressed miRNAs in RASFs versus osteoarthritis (OA) SFs were identified by Real-time PCR-based miRNA screening of 260 individual miRNAs. Transfection of precursor miRNAs pre-miR-203 was used to analyze the function of miR-203 in RASFs. Levels of IL-6 and matrix-metalloproteinases were measured by Real-time PCR and ELISA. RASFs were stimulated with IL-1β, TNFα, LPS and 5-azacytidine. Activity of IkappaB kinase 2 was inhibited with SC-514. RESULTS.: Expression of miR-203 was higher in RASFs than in OASFs or healthy donors. Stimulation with neither IL-1β, TNFα nor LPS changed levels of miR-203, however, DNA demethylation with 5-azacytidine increased the expression of miR-203. Enforced expression of miR-203 led to significantly increased levels of MMP-1 and IL-6. Induction of IL-6 by miR-203 overexpression was inhibited by blocking of the NF-κB pathway. Basal expression levels of IL-6 correlated with basal expression levels of miR-203. CONCLUSION.: In the current study, we demonstrate methylation dependent regulation of miR-203 expression in RASFs. Importantly, we show that elevated levels of miR-203 lead to increased secretion of MMP-1 and IL-6 via the NFkB pathway and thereby contribute to the activated phenotype of synovial fibroblasts in RA. |
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Authors:
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Joanna Stanczyk; Caroline Ospelt; Emmanuel Karouzakis; Andrew Filer; Karim Raza; Christoph Kolling; Renate Gay; Christopher D Buckley; Paul P Tak; Steffen Gay; Diego Kyburz |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2010-10-27 |
Journal Detail:
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Title: Arthritis and rheumatism Volume: - ISSN: 1529-0131 ISO Abbreviation: - Publication Date: 2010 Oct |
Date Detail:
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Created Date: 2010-10-28 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0370605 Medline TA: Arthritis Rheum Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Center of Experimental Rheumatology and Zurich Center of Integrative Human Physiology (ZIHP), University Hospital, Zurich, Switzerland. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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