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Aberrant skeletal muscle-brain communication in sepsis-associated encephalopathy: Elucidating the pathogenic roles of skeletal muscle-derived exosomes

Research Project

Project/Area Number 19KK0224
Research Category

Fund for the Promotion of Joint International Research (Fostering Joint International Research (B))

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 55:Surgery of the organs maintaining homeostasis and related fields
Research InstitutionMie University

Principal Investigator

川本 英嗣  三重大学, 医学部附属病院, 講師 (20577415)

Co-Investigator(Kenkyū-buntansha) 亀井 政孝  三重大学, 医学部附属病院, 教授 (60443503)
赤間 悠一  三重大学, 医学部附属病院, 助教 (40763313)
中森 裕毅  三重大学, 医学部附属病院, 助教 (80815994)
池尻 薫  三重大学, 医学部附属病院, 助教 (90813014)
Project Period (FY) 2019-10-07 – 2024-03-31
Project Status Granted (Fiscal Year 2020)
Budget Amount *help
¥18,200,000 (Direct Cost: ¥14,000,000、Indirect Cost: ¥4,200,000)
Fiscal Year 2023: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Fiscal Year 2022: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2021: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2020: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywordsイリシン / 骨格筋エキソソーム / 細胞外小胞 / マイオカイン / マイオソーム / 敗血症 / PICS / ICU-AW / fMRI / miRNA / 敗血症関連脳症 / エキソソーム / ミオカイン
Outline of Research at the Start

感染症に対する免疫系反応の制御不能による多臓器不全である敗血症(Sepsis)は世界で年間数百万人が罹患し、そのうち4人に1人以上が死亡する.敗血症による中枢神経機能障害である敗血症関連脳症(Sepsis-Associated Encephalopathy)は重要な生命予後不良因子であるが、その病態機序は不明である。
本研究では運動器官である骨格筋の“隠れた機能である内分泌能”を介した中枢神経系制御メカニズム「骨格筋-脳コミュニケーション」に着目し、敗血症関連脳症の病態を解明かつ新規治療標的を同定する。

Outline of Annual Research Achievements

細胞外小胞(Extracellular Vesicle: EV)は、細胞間コミュニケーションの重要な担い手として注目されており、組織間のクロストークを媒介している。筋細胞由来のEVとマイオカインは、細胞の分化、増殖、代謝を司る強力なメディエーターであることがわかってきた。筋細胞由来のEV、マイオカイン、マイクロRNA、サイトカイン、ケモカイン、プロスタグランジンなどの生物学的調節因子は、肝臓や脂肪組織などの重要な部位におけるニッチのリモデリングを調節する可能性がある。
今年度は骨格筋由来のマイオカインの1つであるイリシンに注目し、白血球の相互作用について検証した。その結果、イリシン蛋白と白血球インテグリンの接着について同定した。この結果は骨格筋マイオカインが白血球の接着を調整する可能性を示唆している。

Current Status of Research Progress
Current Status of Research Progress

2: Research has progressed on the whole more than it was originally planned.

Reason

骨格筋由来のエキソソームの抽出に成功した。
さらに骨格筋から放出されるマイオカインの1つであるイリシンと白血球との相互作用について検証した。

Strategy for Future Research Activity

骨格筋マイオカインの1つのイリシンに注目して白血球との相互作用について検討する。さらに血管内皮細胞への影響についても検証を行う。

Report

(2 results)
  • 2020 Research-status Report
  • 2019 Research-status Report

Research Products

(15 results)

All 2021 2020 2019

All Journal Article (15 results) (of which Int'l Joint Research: 7 results,  Peer Reviewed: 15 results,  Open Access: 15 results)

  • [Journal Article] The Spike Glycoprotein of SARS-CoV-2 Binds to β1 Integrins Expressed on the Surface of Lung Epithelial Cells.2021

    • Author(s)
      Park EJ, Myint PK, Appiah MG, Darkwah S, Caidengbate S, Ito A, Matsuo E, Gaowa a, Shimaoka M. Kawamoto E,
    • Journal Title

      Viruses

      Volume: 13 Pages: 645-645

    • DOI

      10.3390/v13040645

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Irisin supports integrin-mediated cell adhesion of lymphocytes.2021

    • Author(s)
      Myint PK, Ito A, Appiah MG, Obeng G, Darkwah S, Kawamoto E, Gaowa A, Park EJ, Shimaoka M
    • Journal Title

      Biochemistry and Biophysics Reports

      Volume: 26 Pages: 100977-100977

    • DOI

      10.1016/j.bbrep.2021.100977

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Remodeling of Bone Marrow Niches and Roles of Exosomes in Leukemia.2021

    • Author(s)
      Yamaguchi T, Kawamoto E, Gaowa A, Park EJ, Shimaoka M.
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 22 Pages: 1881-1881

    • DOI

      10.3390/ijms22041881

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Potential Roles of Muscle-Derived Extracellular Vesicles in Remodeling Cellular Microenvironment: Proposed Implications of the Exercise-Induced Myokine, Irisin2021

    • Author(s)
      Darkwah Samuel、Park Eun Jeong、Myint Phyoe Kyawe、Ito Atsushi、Appiah Michael G.、Obeng Gideon、Kawamoto Eiji、Shimaoka Motomu
    • Journal Title

      Frontiers in Cell and Developmental Biology

      Volume: 9 Pages: 1-1

    • DOI

      10.3389/fcell.2021.634853

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Ligand-competent fractalkine receptor is expressed on exosomes.2021

    • Author(s)
      Park EJ, Myint PK, Appiah MG, Worawattananutai P, Inprasit J, Prajuabjinda O, Soe ZY, Gaowa A, Kawamoto E, Shimaoka M.
    • Journal Title

      Biochemistry and Biophysics Reports

      Volume: 26 Pages: 100932-100932

    • DOI

      10.1016/j.bbrep.2021.100932

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Methods to Study Integrin Functions on Exosomes2020

    • Author(s)
      Kawamoto Eiji、Park Eun Jeong、Shimaoka Motomu
    • Journal Title

      Methods Mol Biol.

      Volume: 2217 Pages: 265-281

    • DOI

      10.1007/978-1-0716-0962-0_15

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Integrin-Ligand Interactions in Inflammation, Cancer, and Metabolic Disease: Insights Into the Multifaceted Roles of an Emerging Ligand Irisin2020

    • Author(s)
      Park Eun Jeong、Myint Phyoe Kyawe、Ito Atsushi、Appiah Michael G.、Darkwah Samuel、Kawamoto Eiji、Shimaoka Motomu
    • Journal Title

      Frontiers in Cell and Developmental Biology

      Volume: 8 Pages: 1-1

    • DOI

      10.3389/fcell.2020.588066

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Targeted remodeling of breast cancer and immune cell homing niches by exosomal integrins.2020

    • Author(s)
      Myint PK, Park EJ, Gaowa A, Kawamoto E, Shimaoka M.
    • Journal Title

      Diagnostic Pathology

      Volume: 15 Pages: 1-1

    • DOI

      10.1186/s13000-020-00959-3

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Exosomes in Sepsis and Inflammatory Tissue Injury2020

    • Author(s)
      Park EJ, Appiah MG, Myint PK, Gaowa A, 他2名
    • Journal Title

      Current Pharmaceutical Design

      Volume: 25 Pages: 4486-4495

    • DOI

      10.2174/1381612825666191116125525

    • Related Report
      2020 Research-status Report 2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Feasibility of Measuring Face-to-Face Interactions among ICU Healthcare Professionals Using Wearable Sociometric Badges2020

    • Author(s)
      Ito-Masui Asami、Kawamoto Eiji、Nagai Yuki、Takagi Yuto、Ito Mami、Mizutani Noriko、Yano Ken’ichi、Yano Kazuo、Imai Hiroshi、Shimaoka Motomu
    • Journal Title

      Am J Respir Crit Care Med.

      Volume: 201 Pages: 245-247

    • DOI

      10.1164/rccm.201904-0779le

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Differential Roles of Dendritic Cells in Expanding CD4 T Cells in Sepsis2019

    • Author(s)
      Darkwah Samuel、Nago Nodoka、Appiah Michael G.、Myint Phyoe Kyawe、Kawamoto Eiji、Shimaoka Motomu、Park Eun Jeong
    • Journal Title

      Biomedicines

      Volume: 7 Pages: 52-52

    • DOI

      10.3390/biomedicines7030052

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Talin-2 regulates integrin functions in exosomes2019

    • Author(s)
      Soe Zay Yar、Prajuabjinda Onmanee、Myint Phyoe Kyawe、Gaowa Arong、Kawamoto Eiji、Park Eun Jeong、Shimaoka Motomu
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 512 Pages: 429-434

    • DOI

      10.1016/j.bbrc.2019.03.027

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Anti-adhesive effects of human soluble thrombomodulin and its domains2019

    • Author(s)
      Kawamoto Eiji、Nago Nodoka、Okamoto Takayuki、Gaowa Arong、Masui-Ito Asami、Sakakura Yosuke、Akama Yuichi、Soe Zay Yar、Prajuabjinda Onmanee、Darkwah Samuel、Appiah Michael G.、Myint Phyoe Kyawe、Obeng Gideon、Park Eun Jeong、Imai Hiroshi、Shimaoka Motomu
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 511 Pages: 312-317

    • DOI

      10.1016/j.bbrc.2019.02.041

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Connexins and Integrins in Exosomes2019

    • Author(s)
      Shimaoka M, Kawamoto E, Gaowa A, Okamoto T, Park EJ
    • Journal Title

      Cancers

      Volume: - Pages: 106-106

    • DOI

      10.3390/cancers11010106

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Integrin and PD-1 Ligand Expression on Circulating Extracellular Vesicles in Systemic Inflammatory Response Syndrome and Sepsis2019

    • Author(s)
      Kawamoto Eiji、Masui-Ito Asami、Eguchi Akiko、Soe Zay Yar、Prajuabjinda Onmanee、Darkwah Samuel、Park Eun Jeong、Imai Hiroshi、Shimaoka Motomu
    • Journal Title

      Shock.

      Volume: - Pages: 1-1

    • DOI

      10.1097/shk.0000000000001228

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research

URL: 

Published: 2019-10-10   Modified: 2021-12-27  

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