| Project/Area Number |
16K09889
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Collagenous pathology/Allergology
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
Mizoguchi Fumitaka 東京医科歯科大学, 大学院医歯学総合研究科, 助教 (60510360)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2016: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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| Keywords | 関節リウマチ / 線維芽細胞 / 滑膜組織 / 滑膜線維芽細胞 / トランスクリプトミクス / 病理学 / 免疫学 |
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| Outline of Final Research Achievements |
We have reported that synovial fibroblasts consist of three major subsets with distinct functions. One fibroblast subset, characterized by CD34-THY1+, is expanded in patients with rheumatoid arthritis (RA) compared to those with osteoarthritis. These fibroblasts are proliferative, express high level of proteinases and RANKL, a crucial cytokine for osteoclastogenesis, and have a phenotype characteristic of invasive cells, indicating the pathogenic roles in RA. CD34+ subset is characterized by the high expression of inflammatory cytokines.
To identify candidate target genes for the development of fibroblast-targeting therapy, we focused on the differentially expressed transcription factors (TFs) across fibroblast subsets. We performed in vitro assays using siRNAs to knock down the expression of the TFs, and found new TFs to regulate the fibroblast functions.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究により、RA関連滑膜線維芽細胞サブセットの機能や増生を抑えることを作用機序とする、新たな治療戦略の開発へとつながることが期待される。このような治療は既存の治療薬によっても改善が得られない患者や、合併症のために治療が困難な患者への選択肢として、RA診療の抱える課題の克服へとつながることが期待される。
更に、線維芽細胞は間質性肺炎や肝硬変、慢性腎不全など数多くの炎症性疾患や慢性の臓器障害をきたす疾患において重要な役割を担うことが知られており、線維芽細胞による疾患制御という新たな領域を切り開く成果になると考えられる。
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