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microRNA as a target to develop a novel treatment for rheumatoid arthritis and to clarify a new pathology in rheumatoid arthritis

Research Project

Project/Area Number 24591443
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field 膠原病・アレルギー・感染症内科学
Research InstitutionTokyo 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.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • 2012 Research-status Report
  • Research Products

    (1 results)

All 2014

All Presentation (1 results)

  • [Presentation] 転写抑制因子ets variant 6の発現を抑制するmicroRNAの阻害は、 関節リウマチ滑膜線維芽細胞からの matrix metalloproteinase-3とinterleukin-6産生を抑制する2014

    • Author(s)
      長谷川久紀、溝口史高、宮坂信之、上阪等
    • Organizer
      第42回日本臨床免疫学会総会
    • Place of Presentation
      京王プラザホテル(東京都新宿)
    • Year and Date
      2014-09-25 – 2014-09-27
    • Related Report
      2014 Annual Research Report

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Published: 2013-05-31   Modified: 2019-07-29  

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