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Comprehensive identification of responsible regulatory molecules that define the seizure periodicity and inflammatory diversity of autoinflammatory diseases

Research Project

Project/Area Number 20H03719
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 54020:Connective tissue disease and allergy-related
Research InstitutionEhime University

Principal Investigator

Masumoto Junya  愛媛大学, プロテオサイエンスセンター, 教授 (20334914)

Co-Investigator(Kenkyū-buntansha) 吉浦 孝一郎  長崎大学, 原爆後障害医療研究所, 教授 (00304931)
竹田 浩之  愛媛大学, プロテオサイエンスセンター, 准教授 (40609393)
澤崎 達也  愛媛大学, プロテオサイエンスセンター, 教授 (50314969)
右田 清志  福島県立医科大学, 医学部, 教授 (60264214)
堀内 浩幸  広島大学, 統合生命科学研究科(生), 教授 (80243608)
川上 純  長崎大学, 医歯薬学総合研究科(医学系), 教授 (90325639)
古賀 智裕  長崎大学, 医歯薬学総合研究科(医学系), 助教 (90537284)
Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥17,680,000 (Direct Cost: ¥13,600,000、Indirect Cost: ¥4,080,000)
Fiscal Year 2022: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2021: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
Fiscal Year 2020: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000)
Keywords自己炎症疾患 / インフラマソーム / 周期熱症候群 / ヒトタンパク質アレイ / 24k-HUPA
Outline of Research at the Start

本研究は、『自己炎症疾患責任タンパク質の周囲で働く未知の協働分子群が疾患のトリガーや炎症発作の周期性を規定し、それらの分子の組織局在が病態を規定する』いう仮説を検証し、自己炎症疾患の原因を単一分子の遺伝子変異に限定することなく、一塊の分子群の異常として再定義する。これにより、その分子群全体を標的とする分子標的治療法の開発につながり、自己炎症疾患の正確な診断と適切な時期における適切な治療である治療機会の窓(”Window of opportunity” (O'Dell JR. Arthritis Rheum. 2002))を開き、自己炎症疾患患者の生活の質の向上と予後の改善に寄与する。

Outline of Final Research Achievements

In this study, we used a human protein array based on wheat-germ cell-free protein synthesis system to identify several proteins that interact and cooperate with the gene products responsible for autoinflammatory diseases. We performed a comprehensive death domain superfamily proteins involved in signaling that orchestrate with the gene products responsible for autoinflammatory diseases. In addition, we conducted individual validation experiments using model mice. Finally, we clarifed the relationship between amyloid fibril formation and inflammasome formation as one of the candidates for triggering inflammatory attacks.

Academic Significance and Societal Importance of the Research Achievements

自己炎症疾患は、自己抗体や自己反応性T細胞の介在しない炎症疾患で、単一の責任遺伝子のコードする疾患責任タンパク質の機能異常が原因とされている。しかしながら、『自己炎症疾患の炎症発作にはどのような分子群や環境因子が関わって全体像を構成しているのか?』という本研究課題の核心をなす学術的「問い」について明確な答えはない。本研究では、自己炎症疾患責任タンパク質の周囲で働く未知の協働分子をいくつか同定することができた。この研究成果は、これらの分子が周期性炎症の鍵を握る分子である可能性を示したという学術的意義を有すると同時に、これらの分子を標的とした治療や診断への応用が期待できるという社会的意義を有する。

Report

(4 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Annual Research Report
  • 2020 Annual Research Report
  • Research Products

    (24 results)

All 2023 2022 2021 2020 2019 Other

All Journal Article (12 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 12 results,  Open Access: 11 results) Presentation (10 results) (of which Invited: 2 results) Remarks (1 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Intestinal edema induced by LPS-induced endotoxemia is associated with an inflammasome adaptor ASC2023

    • Author(s)
      Yamamoto Toshihiro、Kurata Mie、Kaneko Naoe、Masumoto Junya
    • Journal Title

      PLOS ONE

      Volume: 18 Issue: 2 Pages: e0281746-e0281746

    • DOI

      10.1371/journal.pone.0281746

    • Related Report
      2022 Annual Research Report 2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Expression of factor XIII originating from synovial fibroblasts and macrophages induced by interleukin-6 signaling2023

    • Author(s)
      Hirofumi Watanabe & Sho Mokuda, Tadahiro Tokunaga, Hiroki Kohno, Michinori Ishitoku, Kei Araki, Tomohiro Sugimoto, Yusuke Yoshida, Toshihiro Yamamoto, Mayuko Matsumoto, Junya Masumoto, Shintaro Hirata, Eiji Sugiyama
    • Journal Title

      Inflammation and Regeneration

      Volume: 43 Issue: 1 Pages: 2-2

    • DOI

      10.1186/s41232-022-00252-4

    • Related Report
      2022 Annual Research Report 2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Myxoid type and non-myxoid type of intimal sarcoma in large vessels and heart: review of histological and genetic profiles of 20 cases2022

    • Author(s)
      Yamada Yuichi、Fukushima Mana(31名中27番目)
    • Journal Title

      Virchows Archiv

      Volume: 480 Issue: 4 Pages: 919-925

    • DOI

      10.1007/s00428-022-03293-9

    • Related Report
      2022 Annual Research Report 2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Unique Angiogenesis From Cardiac Arterioles During Pericardial Adhesion Formation2022

    • Author(s)
      Namiguchi Kenji、Sakaue Tomohisa、Okazaki Mikio、Kanno Kaho、Komoda Yuhei、Shikata Fumiaki、Kurata Mie、Ota Noritaka、Kubota Yoshiaki、Kurobe Hirotsugu、Nishimura Takashi、Masumoto Junya、Higashiyama Shigeki、Izutani Hironori
    • Journal Title

      Frontiers in Cardiovascular Medicine

      Volume: 8 Pages: 61591-61591

    • DOI

      10.3389/fcvm.2021.761591

    • Related Report
      2022 Annual Research Report 2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Inflammasome assembly is required for intracellular formation of β2-microglobulin amyloid fibrils, leading to IL-1β secretion2022

    • Author(s)
      Kaneko Naoe、Mori Wakako、Kurata Mie、Yamamoto Toshihiro、Zako Tamotsu、Masumoto Junya
    • Journal Title

      International Journal of Immunopathology and Pharmacology

      Volume: 36 Pages: 039463202211045-039463202211045

    • DOI

      10.1177/03946320221104554

    • Related Report
      2022 Annual Research Report 2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A comprehensive interaction study provides a potential domain interaction network of human death domain superfamily proteins2021

    • Author(s)
      Wei Zhou, Naoe Kaneko, Tomoya Nakagita, Hiroyuki Takeda, Junya Masumoto
    • Journal Title

      Cell Death and Differentiation

      Volume: in press

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A single-chain antibody generation system yielding CAR-T cells with superior antitumor function2021

    • Author(s)
      Ochi Toshiki、Maruta Masaki、Tanimoto Kazushi、Kondo Fumitake、Yamamoto Toshihiro、Kurata Mie、Fujiwara Hiroshi、Masumoto Junya、Takenaka Katsuto、Yasukawa Masaki
    • Journal Title

      Communications Biology

      Volume: 4 Issue: 1 Pages: 273-273

    • DOI

      10.1038/s42003-021-01791-1

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The possession of exon 2 or exon 3 variants in the MEFV gene promotes inflammasome activation in Japanese patients with familial Mediterranean fever with a heterozygous exon 10 mutation2020

    • Author(s)
      Yushiro Endo, Tomohiro Koga, Kazusato Hara, Kaori Furukawa, Kazunaga Agematsu, Akihiro Yachie, Junya Masumoto, Kiyoshi Migita, Atsushi Kawakami.
    • Journal Title

      Clin Exp Rheumatol

      Volume: 38 Suppl 127 Pages: 49-52

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Next-generation sequencing of the whole MEFV gene in Japanese patients with familial Mediterranean fever: a case-control association study2020

    • Author(s)
      Tomohiro Koga, Shuntaro Sato, Hiroyuki Mishima, Kiyoshi Migita, Yushiro Endo, Masataka Umeda, Remi Sumiyoshi, Fumiaki Nonaka, Shoichi Fukui, Shin-Ya Kawashiri, Naoki Iwamoto, Kunihiro Ichinose, Mami Tamai, Hideki Nakamura, Tomoki Origuchi, Yukitaka Ueki, Junya Masumoto,et al.
    • Journal Title

      Clin Exp Rheumatol

      Volume: 38 Suppl 127 Pages: 35-41

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] KN3014, a piperidine-containing small compound, inhibits auto-secretion of IL-1β from PBMCs in a patient with Muckle?Wells syndrome2020

    • Author(s)
      Kaneko Naoe、Kurata Mie、Yamamoto Toshihiro、Shigemura Tomonari、Agematsu Kazunaga、Yamazaki Takashi、Takeda Hiroyuki、Sawasaki Tatsuya、Koga Tomohiro、Kawakami Atsushi、Yachie Akihiro、Migita Kiyoshi、Yoshiura Koh-ichiro、Urano Takeshi、Masumoto Junya
    • Journal Title

      Scientific Reports

      Volume: 10 Issue: 1 Pages: 13562-13562

    • DOI

      10.1038/s41598-020-70513-0

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Angiotensin-converting Enzyme 2, a SARS-CoV-2 Receptor, Is Upregulated by Interleukin 6 through STAT3 Signaling in Synovial Tissues.2020

    • Author(s)
      Mokuda S, Tokunaga T, Masumoto J, Sugiyama E.
    • Journal Title

      J Rheumatol.

      Volume: 47 Issue: 10 Pages: 2553-2558

    • DOI

      10.3899/jrheum.200547

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Valve Interstitial Cell-Specific Cyclooxygenase-1 Associated With Calcification of Aortic Valves.2019

    • Author(s)
      Sakaue T, Hamaguchi M, Aono J, Nakashiro KI, Shikata F, Kawakami N, Oshima Y, Kurata M,?Nanba D, Masumoto J, Yamaguchi O, Higashiyama S, Izutani H.
    • Journal Title

      Ann Thorac Surg

      Volume: S0003-4975 Issue: 1 Pages: 31717-5

    • DOI

      10.1016/j.athoracsur.2019.09.085

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] プロテオインタラクトームによる自己炎症疾患の病態解明2022

    • Author(s)
      増本純也
    • Organizer
      111回日本病理学会総会(神戸)2022/4/14-15.
    • Related Report
      2022 Annual Research Report 2021 Annual Research Report
    • Invited
  • [Presentation] エンドトキシン誘発敗血症モデルにおけるインフラマソーム非依存性炎症の組織像2022

    • Author(s)
      山本敏弘、倉田美恵、金子直恵、増本純也
    • Organizer
      第45回日本分子生物学会年会(千葉)2022/11/30-12/2
    • Related Report
      2022 Annual Research Report
  • [Presentation] β2ミクログロブリンのアミロイド線維形成にはインフラマソームの形成が必須である2022

    • Author(s)
      金子直恵、森若子、倉田美恵、山本敏弘、座古保、増本純也
    • Organizer
      第45回日本分子生物学会年会(千葉)2022/11/30-12/2
    • Related Report
      2022 Annual Research Report
  • [Presentation] エンドトキシン誘発敗血症モデルにおけるインフラマソーム非依存性炎症の組織像2022

    • Author(s)
      山本敏弘、倉田美恵、金子直恵、増本純也
    • Organizer
      第45回日本分子生物学会年会(千葉)2022/11/30-12/2.
    • Related Report
      2021 Annual Research Report
  • [Presentation] β2ミクログロブリンのアミロイド線維形成にはインフラマソームの形成が必須である2022

    • Author(s)
      金子直恵、森若子、倉田美恵、山本敏弘、座古保、増本純也
    • Organizer
      第45回日本分子生物学会年会(千葉)2022/11/30-12/2.
    • Related Report
      2021 Annual Research Report
  • [Presentation] 無細胞インフラマソーム再構成系による自己炎症疾患に対する分子標的薬の開発2021

    • Author(s)
      増本純也, 金子直恵, 倉田美恵, 山本敏弘, 重村倫成, 上松一永, 山崎崇志, 谷内江昭宏, 浦野健, 右田清志, 吉浦 孝一郎, 古賀智裕, 川上純.
    • Organizer
      第4回日本免疫不全・自己炎症学会総会・学術集会 2021年 2月6~7日
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] 無細胞NLRP3インフラマソーム再構成系によるMuckle-Wells症候群に対する分子標的薬の開発2020

    • Author(s)
      増本純也, 重村倫成, 重村倫成, 上松一永, 山崎崇志, 谷内江昭宏, 浦野健, 右田清志, 吉浦孝一郎, 古賀智裕, 川上純.
    • Organizer
      第64回日本リウマチ学会総会・学術集会 , 2020年 8月17日~9月15日
    • Related Report
      2020 Annual Research Report
  • [Presentation] インフラマソーム病に対する特異的低分子阻害薬の探索と分子病理診断への応用2020

    • Author(s)
      増本純也, 金子直恵, 倉田美恵, 山本敏弘, 森川紳之祐, 竹田浩之, 澤崎達也, 重村倫成, 上松一永.
    • Organizer
      第109回日本病理学会 2020年 4月16~18日
    • Related Report
      2020 Annual Research Report
  • [Presentation] 無細胞合成タンパク質アレイと AlphaScreenを用いたヒ ト Death Domain-fold Superfamilyインタラクトームの 網羅的研究2020

    • Author(s)
      Wei Zhou, 竹田浩之, 中北智哉, 金子直恵, 増本純也.
    • Organizer
      第93回日本生化学会大会 2020年 9月14日~16日
    • Related Report
      2020 Annual Research Report
  • [Presentation] A Comprehensive Analysis of Human Death Domain-fold Superfamily Interactome Using Recombinant Protein Array and AlphaScreen2020

    • Author(s)
      Wei Zhou, Tomoya Nagagita, Naoe Kaneko, Hiroyuki Takeda, Junya Masumoto
    • Organizer
      第20回日本蛋白質科学会年会 2020年 7月28日
    • Related Report
      2020 Annual Research Report
  • [Remarks] コムギ胚芽無細胞再構成系で稀少難病の治療薬候補を開発

    • URL

      https://www.ehime-u.ac.jp/data_relese/data_relese-129613/

    • Related Report
      2020 Annual Research Report
  • [Patent(Industrial Property Rights)] マックルウェルズ症候群の治療用医薬組成物2020

    • Inventor(s)
      増本純也、金子直恵、澤崎達也、竹田浩之
    • Industrial Property Rights Holder
      愛媛大学
    • Industrial Property Rights Type
      特許
    • Filing Date
      2020
    • Acquisition Date
      2022
    • Related Report
      2022 Annual Research Report 2021 Annual Research Report

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Published: 2020-04-28   Modified: 2024-01-30  

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