| Project/Area Number |
18K19418
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| Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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| Allocation Type | Multi-year Fund |
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| Review Section |
Medium-sized Section 48:Biomedical structure and function and related fields
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| Research Institution | University of Nagasaki (2020)
Gunma University (2018-2019) |
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Principal Investigator |
Shibasaki Koji 長崎県立大学, 看護栄養学部, 教授 (20399554)
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| Project Period (FY) |
2018-06-29 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2019: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2018: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
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| Keywords | TRPV2 / メカノセンサー / 温度 / 網膜剥離 / 機械刺激 / TRPV4 / 神経 / リハビリ / 発生 / TRPチャネル / 軸索伸長 / 発熱 |
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| Outline of Final Research Achievements |
The passive stretching-dependent axonal outgrowth occurs in our body. It has
never been identified for a long time which molecules are the mechanosensors for it. We previously reported that TRPV2 was a mechanosensor channel which contributed axonal outgrowth in membrane stretch dependent manner. These results indicate that TRPV2 might be an important component for passive stretching under specific intracellular temperature, if TRPV2 can detect very weak mechanical stimulus at higher intracellular temperature. In this study, we examined whether TRPV2 can detect such very weak mechanical stimulus under specific intracellular temperature by a Ca2+-imaging method and a whole-cell patch clamp recording. We also examined whether the activation of TRPV2 by weak mechanical stimulus lead to the enhancement of axonal outgrowth. Finally, we identified that TRPV2 had a potential to detect very weak mechanical stimulus only under specific intracellular temperature.
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| Academic Significance and Societal Importance of the Research Achievements |
本知見を応用して、病態原因解明の研究にも取り組んだ。TRPV2の類縁分子であり、TRPV2同様にメカノセンサー、温度センサーとして機能するTRPV4に着目し、網膜剥離の病態悪化機構を解析した。網膜剥離は強度の近視や糖尿病、ボクサーのように眼に強い刺激を受けることにより発症する。年間１万人に１人が発症すると考えられており、誰もが患者になる可能性がある失明を伴う重篤な疾患である。しかしながら、どのような分子メカニズムで病態悪化が進行するのかよく分かっていなかった。今回、研究実施者の研究からそのメカニズムの全貌が明らかとなり、新たな治療法を見出した。
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