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Involvement of a lysosomal protein in maintaining nervous/muscular tissues

Research Project

Project/Area Number 17H03930
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Integrative animal science
Research InstitutionThe University of Tokyo

Principal Investigator

NISHIHARA Masugi  東京大学, 大学院農学生命科学研究科(農学部), 教授 (90145673)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥15,990,000 (Direct Cost: ¥12,300,000、Indirect Cost: ¥3,690,000)
Fiscal Year 2019: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2018: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2017: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Keywords生理学 / 神経組織 / 筋組織 / プログラニュリン / リソソーム
Outline of Final Research Achievements

We have found that progranulin (PGRN), which is known to have neuroprotective properties, is a kind of lysosomal proteins. In this study, we investigated the involvement of PGRN in maintaining homeostasis of nervous/muscular tissues. We found that PGRN suppresses excessive excitatory responses of neurons to seizure-inducible drugs, maintains adult hippocampal neurogenesis by attenuating neuroinflammation under acute immune stress, and promotes integrated muscular regeneration by regulating the dynamics of macrophages after muscular injury.

Academic Significance and Societal Importance of the Research Achievements

プログラニュリン(PGRN)は多様な神経保護作用をもつ分子であるが、その受容体や作用機序については不明な点が多い。我々はPGRNがリソソームの酸性化を介してその機能や生合成を調節する新規のリソソームタンパク質であることを示した。さらに、PGRNは神経組織および筋組織の損傷時や病態時に発現が上昇し、神経細胞の興奮性や免疫系細胞の動態等を制御することにより組織の修復や恒常性の維持に重要な役割を果たしていることを明らかにした。これらの知見は神経筋疾患の病態の解明や治療法の開発に資するものである。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • Research Products

    (22 results)

All 2020 2019 2018 2017

All Journal Article (8 results) (of which Peer Reviewed: 8 results,  Open Access: 3 results) Presentation (13 results) (of which Int'l Joint Research: 2 results) Book (1 results)

  • [Journal Article] Convulsive responses to seizure-inducible drugs are exacerbated in progranulin-deficient mice2020

    • Author(s)
      Kuroda M, Matsuwaki T, Tanaka Y, Yamanouchi K, Nishihara M
    • Journal Title

      Neuroreport

      Volume: 31 Issue: 6 Pages: 478-483

    • DOI

      10.1097/wnr.0000000000001425

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Differentiation of skeletal muscle mesenchymal progenitor cells to myofibroblasts is reversible2020

    • Author(s)
      Takeuchi S, Yamanouchi K, Sugihara H, Matsuwaki T, Nishihara M
    • Journal Title

      Animal Science Jornal

      Volume: 91 Issue: 1

    • DOI

      10.1111/asj.13368

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Oxidative stress-mediated senescence in mesenchymal progenitor cells causes the loss of their fibro/adipogenic potential and abrogates myoblast fusion.2018

    • Author(s)
      Sugihara H, Teramoto N, Yamanouchi K, Matsuwaki T, Nishihara M.
    • Journal Title

      Aging

      Volume: in press Issue: 4 Pages: 747-763

    • DOI

      10.18632/aging.101425

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Identification of CCL5/RANTES as a novel contraction-reducible myokine in mouse skeletal muscle.2018

    • Author(s)
      Ishiuchi Y, Sato H, Komatsu N, Kawaguchi H, Matsuwaki T, Yamanouchi K, Nishihara M, Nedachi T.
    • Journal Title

      Cytokine.

      Volume: 108 Pages: 17-23

    • DOI

      10.1016/j.cyto.2018.03.012

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Progranulin deficiency leads to prolonged persistence of macrophages, accompanied with myofiber hypertrophy in regenerating muscle2018

    • Author(s)
      Sugihara H, Miyaji K, Yamanouchi K, Matsuwaki T, Nishihara M.
    • Journal Title

      Journal of Veterinary Medical Science

      Volume: 80 Issue: 2 Pages: 346-353

    • DOI

      10.1292/jvms.17-0638

    • NAID

      130006410814

    • ISSN
      0916-7250, 1347-7439
    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Skeletal muscle cell contraction reduces a novel myokine, chemokine (C-X-C motif) ligand 10 (CXCL10): potential roles in exercise-regulated angiogenesis.2018

    • Author(s)
      Ishiuchi Y, Sato H, Tsujimura K, Kawaguchi H, Matsuwaki T, Yamanouchi K, Nishihara M, Nedachi T.
    • Journal Title

      Biosci Biotechnol Biochem.

      Volume: 82 Issue: 1 Pages: 97-105

    • DOI

      10.1080/09168451.2017.1411778

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Involvement of progranulin in modulating neuroinflammatory responses but not neurogenesis in the hippocampus of aged mice2017

    • Author(s)
      Ma Y, Matsuwaki T, Yamanouchi K, Nishihara M
    • Journal Title

      Experimantal Gerontology

      Volume: 95 Pages: 1-8

    • DOI

      10.1016/j.exger.2017.05.003

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Progranulin protects hippocampal neurogenesis via suppression of neuroinflammatory responses under acute immune stress2017

    • Author(s)
      Ma Y, Matsuwaki T, Yamanouchi K, Nishihara M
    • Journal Title

      Molecular Neurobiology

      Volume: 54 Issue: 5 Pages: 3717-3728

    • DOI

      10.1007/s12035-016-9939-6

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Presentation] NMDA受容体発現制御機構に対するプログラニュリンの関与2019

    • Author(s)
      黒田万智、松脇貴志、山内啓太郎、西原真杉
    • Organizer
      第4回プログラニュリン研究会
    • Related Report
      2019 Annual Research Report
  • [Presentation] プログラニュリンによる神経細胞の興奮性制御機構の解析2019

    • Author(s)
      黒田万智、松脇貴志、山内啓太郎、西原真杉
    • Organizer
      第31回日本行動神経内分泌研究会
    • Related Report
      2019 Annual Research Report
  • [Presentation] ベッカー型筋ジストロフィーモデルラット骨格筋における新規ジストロフィンアイソフォームの発現2019

    • Author(s)
      寺本奈保美、山内啓太郎、杉原英俊、松脇貴志、西原真杉
    • Organizer
      第162回日本獣医学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 骨格筋の再生過程におけるプログラニュリンの役割2018

    • Author(s)
      杉原英俊、宮地慧、松脇貴志、山内啓太郎、西原真杉
    • Organizer
      第3回プログラニュリン研究会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 神経細胞の興奮性調節に対するプログラニュリン及びIL-1の関与2018

    • Author(s)
      黒田万智、松脇貴志、山内啓太郎、西原真杉
    • Organizer
      第3回プログラニュリン研究会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Potential role of senescent mesenchymal progenitor cells in the progression of sarcopenia2018

    • Author(s)
      Sugihara H, Teramoto N, Yamanouchi K, Matsuwaki T, Nishihara M
    • Organizer
      FASEB science research conference "Skeletal Muscle Satellite Cells and Regeneration"
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Fibroblastic differentiation of mesenchymal progenitor cells may be reversible2018

    • Author(s)
      Takeuchi S, Yamanouchi K, Matsuwaki T, Nishihara M
    • Organizer
      FASEB science research conference "Skeletal Muscle Satellite Cells and Regeneration"
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 老化間葉系前駆細胞は筋衛星細胞の分化能低下を引き起こす2018

    • Author(s)
      杉原英俊、寺本奈保美、松脇貴志、山内啓太郎、西原真杉
    • Organizer
      第17回日本再生医療学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] ペンチレンテトラゾール誘発キンドリングにおけるアストログリオーシスに対するIL-1シグナリングの関与2017

    • Author(s)
      黒田万智、大島拓真、松脇貴志、山内啓太郎、Fang-Chia Chang、西原真杉
    • Organizer
      第160回日本獣医学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Roles of progranulin in regulating hippocampal neurogenesis and neuroinflammatory responses in aged mice2017

    • Author(s)
      Ma Y, Matsuwaki T, Yamanouchi K, Nishihara M
    • Organizer
      The 40th Annual Meeting of the Japan Neuroscience Society
    • Related Report
      2017 Annual Research Report
  • [Presentation] プログラニュリンのアストロサイト特異的エストロゲン受容体発現に対する関与2017

    • Author(s)
      道家未央、松脇貴志、山内啓太郎、西原真杉
    • Organizer
      第2回プログラニュリン研究会
    • Related Report
      2017 Annual Research Report
  • [Presentation] プログラニュリンが薬物誘導性てんかん様発作に与える影響2017

    • Author(s)
      黒田万智、松脇貴志、山内啓太郎、西原真杉
    • Organizer
      第2回プログラニュリン研究会
    • Related Report
      2017 Annual Research Report
  • [Presentation] ノックアウトマウスを用いたプログラニュリン脳内作用の研究2017

    • Author(s)
      松脇貴志、馬 彦博、山内啓太郎、西原真杉
    • Organizer
      第2回プログラニュリン研究会
    • Related Report
      2017 Annual Research Report
  • [Book] Progranulin and Central Nervous System Disorders2019

    • Author(s)
      Nishihara M
    • Total Pages
      183
    • Publisher
      Springer
    • ISBN
      9789811361852
    • Related Report
      2019 Annual Research Report

URL: 

Published: 2017-04-28   Modified: 2021-02-19  

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