2022 Fiscal Year Final Research Report
Non-permeation function of TRPM2 channel complexes and its physiological relevance
Project/Area Number |
19H03417
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Review Section |
Basic Section 48040:Medical biochemistry-related
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Research Institution | Kyoto University |
Principal Investigator |
Mori Yasuo 京都大学, 工学研究科, 教授 (80212265)
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Project Period (FY) |
2019-04-01 – 2022-03-31
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Keywords | イオンチャネル / TRPチャネル / シグナル伝達 / マクロファージ / 炎症 / カルシウム / 活性酸素種 |
Outline of Final Research Achievements |
TRP proteins form cation-permeable channels activated in response to different environmental cues. To transcend this conventional understanding of so-called channel proteins, we studied mechanistic bases and physiological significance of "non-channel function" of TRPM2 activated by H2O2. STAT3 proteins, which were found to interact directly with TRPM2 through an exhaustive screening of associated proteins, nearly abolished TRPM2 activity when co-expressed, and these two proteins severely suppressed the expression levels of each other. In a tumor-bearing model applied to TRPM2 KO mice, the STAT3 signaling cascade was promoted in tumor-associated macrophages and excessive angiogenesis was elicited, while in the drug-induced inflammation model, inflammatory phenotypes were suppressed in TRPM2 KO mice. Thus, we discovered a novel function of TRPM2 that regulates polarization of macrophages via inhibition of STAT3 signals.
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Free Research Field |
分子生理学
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Academic Significance and Societal Importance of the Research Achievements |
地球的規模で自然環境や生態の大きな変化が起きようとしている。ヒトがこういった変化にどう適応するべきかの方策を考えていくためには、生物体が備える環境対応能力を理解する必要がある。本研究が対象としたTRPチャネルは、生体内外環境の化学的・物理学的変化のセンサーとして働くことが知られた陽イオンチャネルであることから、このような課題の解明に最もふさわしい題材を提供する。また、生態系の破壊により顕在化する未体験のウイルスや病原微生物も問題になっており、これらからの生体防御の理解にも本研究は重要なきっかけを与える。
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