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Hypoxia induced factor 1 alpha participates in Schwann cells differentiation in peripheral nerves.

Research Project

Project/Area Number 16K10990
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Anesthesiology
Research InstitutionNational Center of Neurology and Psychiatry

Principal Investigator

Ujiie Yuka  国立研究開発法人国立精神・神経医療研究センター, 神経研究所 疾病研究第五部, 流動研究員 (20511562)

Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords末梢神経 / 髄鞘化 / シュワン細胞 / in vitro myelination / 低酸素誘導因子 / 髄鞘形成 / HIF-1alpha / ミエリン形成 / 末梢神経障害 / 神経再生
Outline of Final Research Achievements

Schwann cell (SC) differentiation plays an important role in PNS myelination. However, underlying mechanisms of SC differentiation remain unclear. Here, we investigated the role of HIF1α in PNS myelination. Culturing in hypoxia or overexpression of HIF1α bearing mutation to be resistant to proteasomal degradation resulted in upregulation of myelin related gene expressions in SCs. Expression of HIF1α in SC increased during development of peripheral nerves. HIF1α stabilizing drug that inhibits prolyl hydroxylation was able to upregulate myelin protein expression and promoted myelination in culture. Transient hypoxic incubation also facilitated in vitro myelination. Expression of HIF1α was also observed in SC in peripheral nerves after injury. The number of myelinating axons was increased by a local application of a HIF1α stabilizing drug. Collectively, HIF1α might be involved in SC differentiation and peripheral myelination during development as well as regeneration after injury.

Academic Significance and Societal Importance of the Research Achievements

末梢神経の髄鞘形成にはシュワン細胞の分化制御が重要であるが、髄鞘化までのシュワン細胞分化制御に関わる分子機構の全貌は未だ不明である。出生によって胎児を取り巻く酸素環境は大きく変化することから,酸素環境の変化がミエリン形成を誘導する可能性に着目した。また、末梢神経発達期の髄鞘化に関わる遺伝子スクリーニング解析結果からHIF1αを見出した。シュワン細胞におけるHIF1αの生理的役割を明らかにし、発生・発達および病態の観点から、末梢神経髄鞘化におけるHIF1α重要性について精査することで、シュワン細胞の分化制御機構および末梢神経障害病態における分子基盤の解明にも貢献すると考えられる。

Report

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

    (5 results)

All 2019 2018 2017 Other

All Journal Article (1 results) (of which Peer Reviewed: 1 results) Presentation (3 results) Remarks (1 results)

  • [Journal Article] 低酸素応答による末梢神経の髄鞘形成制御2018

    • Author(s)
      氏家 悠佳、若月 修二、荒木 敏之
    • Journal Title

      日本応用酵素協会誌

      Volume: 53 Pages: 27-32

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Presentation] 末梢神経のシュワン細胞分化における低酸素誘導因子の関与2019

    • Author(s)
      氏家 悠佳、若月 修二、荒木 敏之
    • Organizer
      第92回日本薬理学会年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Hypoxia-induced factor 1 alpha promotes myelination during development of the peripheral nervous system.2018

    • Author(s)
      Yuka Ujiie, Shuji Wakatuki, Toshiyuki Araki.
    • Organizer
      第41回日本神経科学大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 末梢神経髄鞘化における低酸素応答系の関与2017

    • Author(s)
      氏家悠佳、若月修二、荒木敏之
    • Organizer
      第137回日本薬理学会槓子部会
    • Related Report
      2017 Research-status Report
  • [Remarks] 国立精神・神経医療研究センター疾病研究第5部HP

    • URL

      http://www.ncnp.go.jp/nin/guide/r5/

    • Related Report
      2016 Research-status Report

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Published: 2016-04-21   Modified: 2020-03-30  

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