Critical role of 14-3-3 eta in pathogenesis of rheumatoid arthritis
Project/Area Number |
16K09914
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Collagenous pathology/Allergology
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Research Institution | University of Occupational and Environmental Health, Japan |
Principal Investigator |
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Co-Investigator(Kenkyū-buntansha) |
田中 良哉 産業医科大学, 医学部, 教授 (30248562)
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Research Collaborator |
Trimova Gluzhan
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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: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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Keywords | 関節リウマチ / マクロファージ / 14-3-3η / PAD4 / シトルリン化 / TNF-α / ネクロプトーシス / 関節液 / PADI4 / 14-3-3 eta / 破骨細胞 / 骨破壊 / 免疫学 |
Outline of Final Research Achievements |
Previous study shows that 14-3-3η is detected in the joint fluid of patients with rheumatoid arthritis, and induces inflammation. In this study, we found that macrophage (MΦ) is a main source of extracellular 14-3-3η. Further, TNF-α induced MΦ to suffer from cell death like necropthosis characterized by expanded cell organelles and destroyed cell membranes. As a result, 14-3-3η was secreted into extracellular space. We found the novel mechanism in the affected tissues of patients with RA.
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Academic Significance and Societal Importance of the Research Achievements |
14-3-3ηは生理的状況下で細胞内に局在するが、病的状況下で細胞外でも検出される。TNF-αによる刺激を受けると、MΦがネクロプトーシスを誘導し、細胞外に14-3-3ηを放出する新規メカニズムの解明が、学術的意義である。 RAは働き盛りの年代において発症するが、必ずしも生物学的製剤が奏功するわけではない。本研究により見出されたメカニズムを介して細胞外に放出された14-3-3ηは炎症惹起を齎すので、14-3-3ηを標的にした薬剤の開発により治療応用へ展開する可能性があり、社会的意義が大きいと考える。
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Report
(4 results)
Research Products
(23 results)
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[Journal Article] Relevance of interferon-gamma in pathogenesis of life-threatening rapidly progressive interstitial lung disease in patients with dermatomyositis.2018
Author(s)
Ishikawa Y, Iwata S, Hanami K, Nawata A, Zhang M, Yamagata K, Hirata S, Sakata K, Todoroki Y, Nakano K, Nakayamada S, Satoh M, Tanaka Y.
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Journal Title
Arthritis Res Ther
Volume: 20
Issue: 1
Pages: 240-240
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Spontaneous differentiation of human mesenchymal stem cells on poly-lactic-co-glycolic acid nano-fiber scaffold2016
Author(s)
Koshiro Sonomoto, Kunihiro Yamaoka, Hiroaki Kaneko, Kaoru Yamagata, Kei Sakata, Xiangmei Zhang, Masahiro Kondo, Yukichi Zenke, Ken Sabanai, Shingo Nakayamada, Akinori Sakai, Yoshiya Tanaka
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Journal Title
PLOS ONE
Volume: in press
Issue: 4
Pages: e0153231-e0153231
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Presentation] TNF-ALPHA INDUCES NECROPTOSIS-LIKE DEATH OF MACROPHAGES AND PROMOTES EXTRACELLULAR RELEASE OF 14-3-3ETA2019
Author(s)
Gulzhan Trimova, Kaoru Yamagata, Shigeru Iwata, Tony Zhang, Fumi Uemura, Minoru Satoh, Michelle Zaharik, Norma Biln, Shintaro Hirata, Shingo Nakayamada, Yoshiya Tanaka
Organizer
Annual European Congress of Rheumatology EULAR 2019
Related Report
Int'l Joint Research
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