Epigenetic aberration and pathologic analysis in peripheral blood of adult-onset still's disease
Project/Area Number |
16K09902
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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 | Saitama Medical University |
Principal Investigator |
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Research Collaborator |
KUROKAWA riki
NOMA hisashi
ARAKI yasuto
KUROSAWA natsuko
AIZAKI yoshimi
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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 |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2017: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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Keywords | エピジェネティクス / ヒストンメチル化 / エピジェティクス / 成人スティル病 / ヒストン修飾 / エピゲノム / 内科 / 免疫学 / 末梢血 |
Outline of Final Research Achievements |
1) Histone modification in peripheral blood nucleated cells from adult-onset Still's disease (AOSD) was detected by flow cytometric analysis using specific antibodies against H3K4me3 or H3K27me3. There were specific aberrations of histone methylation in monocytes, neutrophils and B cells from AOSD patients comparing with healthy controls or other disease controls. Of interest was these histone methylation abnormalities were significantly associated with disease activity. Additionally aberrant histone methylations of a specific subset of monocyte with CD14++CD16- were significantly correlated with serum IL-18 concentration. 2) To analyze the pathogenic mechanism of AOSD from epigenetic point of view, ATAC-Seq was performed to identify genes with open chromatins. However, the technique showed nothing and an alternative method was carried out. We made transcriptome analysis and found several candidates of the target genes. We now preparing for ChIP-Seq analysis for the purpose above.
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Academic Significance and Societal Importance of the Research Achievements |
この研究においては、病気の原因の不明な成人発症スチル病(AOSD)の原因を解明するために、血液中の白血球のエピゲノム異常(遺伝子に変化を認めないけれどタンパク質の発現には変化が見られる制御機構)、特にヒストン修飾変化を各細胞亜群毎に解明する研究で、私達は単球という細胞群においてヒストンのメチル化異常を認めた。さらに、このメチル化異常の結果、どのような遺伝子の発現に変化が見られるのかを明らかにした。それを基に、この結果が蛋白の発現に影響するのか、そしてどのように病気の状態に関与するのか現在も研究を進めています。これが明らかになれば、新規治療法の開発に繋がる。
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Report
(4 results)
Research Products
(59 results)
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[Journal Article] Urinary levels of the leukocyte surface molecule CD11b associate with glomerular inflammation in lupus nephritis.2019
Author(s)
Kitagawa A, Tsuboi N, Yokoe Y, Katsuno T, Ikeuchi H, Kajiyama H, Endo N, Sawa Y, Suwa J, Sugiyama Y, Hachiya A, Mimura T, Hiromura K, Maruyama S.
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Journal Title
Kidney Int.
Volume: 95(3)
Issue: 3
Pages: 680-692
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Altered gene expression profiles of histone lysine methyltransferases and demethylases in rheumatoid arthritis synovial fibroblasts2018
Author(s)
Araki, Y., Aizaki, Y., Sato, K., Oda, H., Kurokawa, R., Mimura, T
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Journal Title
Clin Exp Rheumatol
Volume: 36
Pages: 314-316
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] The correlation of urinary podocytes and podocalyxin with histological features of lupus nephritis.2018
Author(s)
Ikuma D, Hiromura K, Kajiyama H, Suwa J, Ikeuchi H, Sakairi T, Kaneko Y, Maeshima A, Kurosawa H, Hirayama Y, Yokota K, Araki Y, Sato K, Asanuma YF, Akiyama Y, Hara M, Nojima Y, Mimura T
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Journal Title
Lupus
Volume: 27
Issue: 3
Pages: 484-493
DOI
Related Report
Peer Reviewed
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[Presentation] Retrospective Analysis of 30 Patients with Limited Cutaneous Systemic Sclerosis for 20 Years.2018
Author(s)
Akiyama, Y., Yoshida, Y., Yokota, K., Araki, Y., Funakubo, Y., Sato, K., Mimura, T
Organizer
11th International Congress on Autoimmunity.
Related Report
Int'l Joint Research
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[Presentation] The Comparative Observational Study about Efficacy, Safety and Adherence between Tocilizumab and Infliximab in Patients with Rheumatoid Arthritis.2018
Author(s)
Matsuda, M., Funakubo Asanuma, Yu., Nakao, Y., Yazawa, H,, Tsuzuki Wada, T., Kouzu, N., Mimura, T
Organizer
2018 ACR/ARHPAnnual Meeting.
Related Report
Int'l Joint Research
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[Presentation] The Efficacy, Safety and Adherence of Biologicbiological Disease-Modifying Anti Rheumatic Drugs, Infliximab, Tocilizumab and Abatacept, in Elderly Patients with Rheumatoid Arthritis.2018
Author(s)
Tsuzuki Wada, T., Funakubo Asanuma, Yu., Matsuda, M., Yazawa, H., Nakao, Y., Kozu, N., Mimura, T
Organizer
2018 ACR/ARHPAnnual Meeting.
Related Report
Int'l Joint Research
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[Presentation] Detection of Precursors of RANK- Osteoclast-like Cells (Olcs) in Peripheral Blood and Olcs in Bone Tissue from Rheumatoid Arthritis Patients.2018
Author(s)
Yokota, K., Tanaka, S., Sekikawa, M., Aizaki, Y., Sato, K., Oda, H., Mimura, T
Organizer
2018 ACR/ARHPAnnual Meeting.
Related Report
Int'l Joint Research
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[Presentation] Presence of RANK-Osteoclast-like Cells in the Bone of Patients with Rheumatoid Arthritis.2018
Author(s)
Yokota, K., Tanaka, S., Sato, K., Aizaki, Y., Oda, H., Mimura, T
Organizer
第62回日本リウマチ学会総会・学術集会
Related Report
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[Presentation] Altered profiles of histone lysine Methylation affect MMP gene transcription in rheumatoid arthritis synovial fibroblasts2016
Author(s)
Y.Araki, T.T.Wada, Y.Aizaki, H.Kajiyama, K.Yokota, K.Sato, Y.F.Asanuma, Y.-T.Kim, H.Oda, T.Mimura
Organizer
EULAR 2016
Place of Presentation
London, UK
Year and Date
2016-06-10
Related Report
Int'l Joint Research
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