2019 Fiscal Year Final Research Report
Basic research for the development of new preventive and therapeutic methods for vascular diseases targeting GM1
| Project/Area Number |
16K08263
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Biological pharmacy
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| Research Institution | Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology |
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Principal Investigator |
Sasaki Norihiko 地方独立行政法人東京都健康長寿医療センター(東京都健康長寿医療センター研究所), 東京都健康長寿医療センター研究所, 研究員 (80639063)
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| Project Period (FY) |
2016-10-21 – 2020-03-31
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| Keywords | 血管内皮細胞 / 老化 / 炎症 / TNFα / GM1ガングリオシド / インスリン抵抗性 / SASP / ラパマイシン |
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| Outline of Final Research Achievements |
In order to examine the effect of inflammatory stimulation, which is a cause of various diseases in individual aging, on vascular endothelial cells, I examined the expression and function of ganglioside after treatment with different concentrations of TNFα for different time intervals for mimicking in vivo acute or chronic inflammatory situations. As a result, it was clarified that the expression of GM1 among various gangliosides was increased dependent on concentration of TNFα and was found to be involved in the decrease in insulin signaling. When exposed to high concentrations of TNFα, GM1 expression-dependent insulin resistance was observed even after removal of TNFα. In this study, we obtained new findings as a molecular mechanism of GM1-regulated vascular insulin resistance.
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| Free Research Field |
基礎老化学
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| Academic Significance and Societal Importance of the Research Achievements |
肥満が増加する中年層から高齢層にかけて生体内では炎症が増加し、動脈硬化を始めとする血管疾患の発症、進展に関わると考えられるが、詳しい分子メカニズムは不明である。今回の成果では、in vitroの血管内皮細胞の炎症モデルを構築し、炎症性サイトカインであるTNFαの濃度や作用期間によってGM1の発現性とインスリン抵抗性との関連が明らかにされた。本研究成果は、加齢性疾患としての血管疾患に対するGM1を標的とした新たな治療法や予防法の開発に向けた基礎となりうるものである。
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