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Role of adapter molecule ASC independent of inflammasome

Research Project

Project/Area Number 16K09521
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Cardiovascular medicine
Research InstitutionToyama Prefectural University

Principal Investigator

Kawanishi Fumitake  富山県立大学, 工学部, 講師 (50585560)

Co-Investigator(Kenkyū-buntansha) 高橋 将文  自治医科大学, 医学部, 教授 (40296108)
唐澤 直義  自治医科大学, 医学部, 助教 (60631893)
木村 博昭  自治医科大学, 医学部, 講師 (70593622)
渡邊 幸子  自治医科大学, 医学部, 助教 (80770619)
Project Period (FY) 2016-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywords炎症 / 免疫 / 生活習慣病 / 血栓症 / 自然免疫
Outline of Final Research Achievements

In this study, we thought that the inflammasome, which is important for inducing aseptic inflammatory reactions such as lifestyle-related diseases, was involved in thrombus formation in venous thrombosis and arterial thrombosis models, clarified its usefulness as a therapeutic target, and regulated inflammasome control. The objective was to construct a new treatment strategy by as a result, it was clarified that in these diseases, ASC molecule contributes to the activation of P-selectin independently of inflammasome and was involved in thrombus formation. In the future, by examining the detailed mechanism of how ASC contributes to the activation of P-selectin, the mechanism of P-selectin regulation by ASC would be clarified, and the pathology of various diseases related to thrombosis and I would like to work on the development of new treatment methods.

Academic Significance and Societal Importance of the Research Achievements

NLRP3インフラマソームは痛風の原因となる尿酸結晶など生体外の無菌的な危険因子を認識し活性化することから注目され、動脈硬化(Nature;464, 2010)や肥満(Cell Metab;12, 2010, Nat Med;17, 2011)といった生活習慣病においても重要な役割を持つことが報告されている。に関してはこれまで血小板におけるインフラマソームの活性化についての報告はあるが(Blood;122, 2013)、血栓形成に直接関与する報告は全くない。本研究により、血栓が関連する様々な疾患の病態解明や新たな治療法の開発に役立つものと考えられる。

Report

(5 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (6 results)

All 2020 2019 2018 2017 2016

All Journal Article (6 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 6 results,  Open Access: 4 results)

  • [Journal Article] Glucose regulates hypoxia-induced NLRP3 inflammasome activation in macrophages.2020

    • Author(s)
      1)Watanabe S, Usui-Kawanishi F, Karasawa, Kimura H, Kamata R, Inoue, Mise N, Kasahara T, Takahashi M
    • Journal Title

      J Cell Physiol

      Volume: - Issue: 10 Pages: 7554-7566

    • DOI

      10.1002/jcp.29659

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Implications of immune-inflammatory responses in smooth muscle dysfunction and disease2019

    • Author(s)
      Usui-Kawanishi Fumitake、Takahashi Masafumi、Sakai Hiroyasu、Suto Wataru、Kai Yuki、Chiba Yoshihiko、Hiraishi Keizo、Kurahara Lin Hai、Hori Masatoshi、Inoue Ryuji
    • Journal Title

      Journal of Smooth Muscle Research

      Volume: 55 Issue: 0 Pages: 81-107

    • DOI

      10.1540/jsmr.55.81

    • NAID

      130007795217

    • ISSN
      0916-8737, 1884-8796
    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Saturated Fatty Acids Undergo Intracellular Crystallization and Activate the NLRP3 Inflammasome in MacrophagesHighlights2018

    • Author(s)
      Karasawa Tadayoshi、Kawashima Akira、Usui-Kawanishi Fumitake、Watanabe Sachiko、Kimura Hiroaki、Kamata Ryo、Shirasuna Koumei、Koyama Yutaro、Sato-Tomita Ayana、Matsuzaka Takashi、Tomoda Hiroshi、Park Sam-Yong、Shibayama Naoya、Shimano Hitoshi、Kasahara Tadashi、Takahashi Masafumi
    • Journal Title

      Arteriosclerosis, Thrombosis, and Vascular Biology

      Volume: 38 Issue: 4 Pages: 744-756

    • DOI

      10.1161/atvbaha.117.310581

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] ARIH2 ubiquitinates NLRP3 and negatively regulates NLRP3 inflammasome activation in macrophages2017

    • Author(s)
      Kawashima Akira、Karasawa Tadayoshi、Tago Kenji、Kimura Hiroaki、Kamata Ryo、Usui-Kawanishi Fumitake、Watanabe Sachiko、Ohta Satoshi、Funakoshi-Tago Megumi、Yanagisawa Ken、Kasahara Tadashi、Suzuki Koichi、Takahashi Masafumi
    • Journal Title

      The Journal of Immunology

      Volume: 199 Issue: 10 Pages: 3614

    • DOI

      10.4049/jimmunol.1700184

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] NLRP3 reduces macrophage interleukin-10 production and enhances the susceptibility to doxorubicin-induced cardiotoxicity.2016

    • Author(s)
      Kobayashi M, Usui F, Karasawa T, Kawashima A, Kimura H, Mizushina Y, Shirasuna K, Mizukami H, Kasahara T, Hasebe N, Takahashi M.
    • Journal Title

      Sci Rep

      Volume: 6 Issue: 1 Pages: 26489-26489

    • DOI

      10.1038/srep26489

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Caspse-1 deficiency promotes high-fat diet-induced adipose tissue inflammation and the development of obesity.2016

    • Author(s)
      Kimura H, Karasawa T, Usui F, Kawashima A, Endo Y, Kobayashi M, Sadatomo A, Nakamura J, Iwasaki Y, T Yada,Tsutsui H, Kasahara T, Takahashi M.
    • Journal Title

      Am J Physiol Endocrinol Metab

      Volume: 311 Issue: 5 Pages: 881-890

    • DOI

      10.1152/ajpendo.00174.2016

    • Related Report
      2016 Research-status Report
    • Peer Reviewed

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Published: 2016-04-21   Modified: 2021-02-19  

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