Hypoxia induced factor 1 alpha participates in Schwann cells differentiation in peripheral nerves.
Project/Area Number |
16K10990
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Anesthesiology
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Research Institution | National 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)
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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.
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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。
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Report
(4 results)
Research Products
(5 results)