Project/Area Number |
24591443
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
膠原病・アレルギー・感染症内科学
|
Research Institution | Tokyo Medical and Dental University |
Principal Investigator |
MIYASAKA Nobuyuki 東京医科歯科大学, 医学部附属病院, 非常勤講師 (30157622)
|
Co-Investigator(Kenkyū-buntansha) |
MIZOGUCHI Fumitaka 東京医科歯科大学, 大学院医歯学総合研究科, 助教 (60510360)
|
Project Period (FY) |
2012-04-01 – 2015-03-31
|
Project Status |
Completed (Fiscal Year 2014)
|
Budget Amount *help |
¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2014: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2013: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2012: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
|
Keywords | 関節リウマチ / microRNA / micro RNA / microRNA阻害剤ライブラリー / Il-6 / MMP-3 |
Outline of Final Research Achievements |
To develop a novel treatment for rheumatoid arthritis (RA), we set a goal to identify microRNAs (miRNA) that control the expression of MMP-3 and IL-6 from RA synovial fibroblasts (RASF) and to clarify the mode of action of the miRNAs in RA through the identification of target genes of the miRNAs. By using a miRNA inhibitor library, we revealed that miR-A inhibitor and miR-B inhibitor suppressed the production of MMP-3 from RASF cultured with TNF-a, respectively. Additionally, miR-A inhibitor suppressed the production of IL-6 from RASF. Gene X, which is a transcription repression factor and suppresses MMP-3 expression, was presumed as the common target gene of miR-A and miR-B from miRNA database analysis. In fact, miR-A inhibitor or miR-B inhibitor suppressed the decrease of protein X expression from RASF cultured with TNF-a. We identified miRNAs that control the expression of MMP-3 and IL-6 from RASF. Inhibition of these miRNAs may be a novel therapeutic strategy for RA.
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