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Activation of hedgehog signal pathway induces peripheral nerve regeneration

Research Project

Project/Area Number 15H05041
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Surgical dentistry
Research InstitutionNiigata University

Principal Investigator

Seo Kenji  新潟大学, 医歯学系, 教授 (40242440)

Co-Investigator(Kenkyū-buntansha) 前田 健康  新潟大学, 医歯学系, 教授 (40183941)
大峡 淳  新潟大学, 医歯学系, 教授 (40266169)
紙谷 義孝  新潟大学, 医歯学系, 准教授 (90381491)
藤原 直士  新潟大学, 医歯学系, 教授 (70181419)
Project Period (FY) 2015-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥16,900,000 (Direct Cost: ¥13,000,000、Indirect Cost: ¥3,900,000)
Fiscal Year 2018: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2017: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2016: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2015: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Keywordshedgehog / peripheral nerve / nerve injury / sonic hedgehog / desrt hedgehog / Gli1 / macrophage / schwann cell / Hedgehog / Sonic / Desert / Indian / 末梢神経損傷 / 歯学 / ヘッジホッグシグナル伝達系 / ソニック / 三叉神経 / Gli-1 / 神経科学 / 再生医学 / 神経再生 / ソニックヘッジホッグ / Patched-1
Outline of Final Research Achievements

Peripheral nerve injury induces expressions of a morphogen Sonic Hedgehog (Shh) and its transcriptional regulator Gli1 in the lesion. Blockade of Shh signaling pathway after peripheral nerve injury leads to abnormal axon growth in random directions, resulting in a disturbance of axonal regeneration. This also increases the number of immature Schwann cell in the medial site of the lesion, but it decreases that of macrophage in the distal site. During the regeneration period, the expression of Shh in the lesion elevates immediately after the injury and attenuates later. In contrast, another homologues Hedgehog family Desert hedgehog (Dhh) exhibits the reverse process. This implicates that nerve injury induces switching the expression of Shh to Dhh and these factors contribute to peripheral nerve regeneration.

Academic Significance and Societal Importance of the Research Achievements

胚発生において形態形成と細胞増殖に働くヘッジホッグシグナル伝達系は、出生後においても末梢神経損傷で誘導され、これらはaxon の慎重に関与してその神経軸索結合・再生に関与する。さらにその中でもソニックヘッジホッグとデザートヘッジホッグは別々に誘導され、それぞれ別々の働きで神経再生に影響する。したがって、末梢神経の再生にはこうした因子の調節が正常な治癒に関与すると考えられる。本研究による結果は、神経種の形成などによる末梢神経再生阻害を予防する方法の開発へ貢献できると期待される。

Report

(5 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Annual Research Report
  • 2016 Annual Research Report
  • 2015 Annual Research Report
  • Research Products

    (5 results)

All 2018 2017 2016 2015

All Journal Article (1 results) (of which Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (4 results) (of which Int'l Joint Research: 2 results)

  • [Journal Article] The Sonic Hedgehog signaling pathway regulates inferior alveolar nerve regeneration.2018

    • Author(s)
      Yamada Y, Ohazama A, Maeda T, Seo K
    • Journal Title

      Neurosci Lett.

      Volume: 671 Pages: 114-119

    • DOI

      10.1016/j.neulet.2017.12.051

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] Possible involvement of hedgehog signal pathway in regeneration afterperipheral nerve injury2017

    • Author(s)
      Y. Yamada, A. Ohazama, T. Maeda and K. Seo
    • Organizer
      10th congress of the European Pain Federation
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Axonal regeneration requires activation of Sonic hedgehog signaling pathway in peripheral nerve injury2016

    • Author(s)
      Y. YAMADA, T. MAEDA, A. OHAZAMA, K. SEO
    • Organizer
      Annual Meeting, Societry for Neuroscience
    • Place of Presentation
      San Diego, USA
    • Year and Date
      2016-11-16
    • Related Report
      2016 Annual Research Report
  • [Presentation] ヘッジホッグシグナル伝達経路の下歯槽神経再生への関与2015

    • Author(s)
      山田友里恵、瀬尾憲司
    • Organizer
      第43回日本歯科麻酔学会総会・学術集会
    • Place of Presentation
      学術総合センター(東京都、千代田区)
    • Year and Date
      2015-10-31
    • Related Report
      2015 Annual Research Report
  • [Presentation] Hedgehog signaling pathway participate in inferior alveolar nerve regeneration2015

    • Author(s)
      Yurie Yamada , Takeyasu Maeda , Kenji Seo
    • Organizer
      Annual meeting, Society for Neuroscience
    • Place of Presentation
      シカゴ、アメリカ合衆国
    • Year and Date
      2015-10-19
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research

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Published: 2015-04-16   Modified: 2020-03-30  

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