Role of histone acetyltransferases in modulation of circadian rhythm in rheumatoid arthritis.
Project/Area Number |
17K16207
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Research Category |
Grant-in-Aid for Young Scientists (B)
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Allocation Type | Multi-year Fund |
Research Field |
Collagenous pathology/Allergology
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Research Institution | Kobe University |
Principal Investigator |
Yoshida Kohsuke 神戸大学, 保健学研究科, 保健学研究員 (80452499)
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Project Period (FY) |
2017-04-01 – 2020-03-31
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Project Status |
Completed (Fiscal Year 2019)
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Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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Keywords | ヒストンアセチル化酵素 / 時計遺伝子 / 関節リウマチ / 炎症性サイトカイン / 日内リズム |
Outline of Final Research Achievements |
We newly found a role of histone acetyltransferases CBP and p300 in rheumatoid arthritis (RA) as follows. In vitro assay using RA-fibroblast like synovial cells, (1) TNF-α, a pro-inflammatory cytokine, induced core clock gene Bmal1 through up-regulating Cbp and p300 gene expression. (2) This induction is cancelled by C646, p300/CBP inhibitor. (3) As well as Bmal1, expression of CCL2 gene,a pro-inflammatory chemokine, is suppressed by C646. In vivo assay using collagen-induced arthritis (CIA) mice, (4) C646-treated mice decreased a arthritis score as compared with DMSO-treated one.
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Academic Significance and Societal Importance of the Research Achievements |
本研究は関節リウマチ患者由来滑膜繊維芽細胞において、TNF-αによる時計遺伝子発現パターンの変調にはヒストンアセチル化酵素が関与している、ことを示した初めての知見である。ヒストンアセチル化酵素阻害薬であるC646は、滑膜細胞の遊走を抑制し関節炎モデルマウスの重症化を抑制させる効果を認めた。これらのことから、ヒストンアセチル化酵素は関節炎の悪化を時計遺伝子を介して軽減することができる可能性が示され、RAの新しい治療標的となることが期待される。
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Report
(4 results)
Research Products
(5 results)
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[Journal Article] Expressions of circadian clock genes represent disease activities of RA patients treated with biological DMARDs.2019
Author(s)
Kaneshiro K, Yoshida K, Morii K, Oketani Y, Uchida K, Yaekura A, Okumura I, Hashimoto T, Kawasaki Y, Shibanuma N, Sakai Y, Hashiramoto A.
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Journal Title
Mod Rheumatol.
Volume: 印刷中
Issue: 2
Pages: 293-300
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] TNF-α induces expression of the circadian clock gene Bmal1 via dual calcium-dependent pathways in rheumatoid synovial cells.2018
Author(s)
Yoshida K, Nakai A, Kaneshiro K, Hashimoto N, Suzuki K, Uchida K, Hashimoto T, Kawasaki Y, Tateishi K, Nakagawa N, Shibanuma N, Sakai Y, Hashiramoto A
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Journal Title
Biochem Biophys Res Commun.
Volume: 495
Issue: 2
Pages: 1675-1680
DOI
Related Report
Peer Reviewed / Open Access
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