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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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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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 / オートファジー / 内皮間葉転換 / 糖脂質 / 透過性 / 接着性 / 内皮細胞 / ガングリオシド / ガングリオシドGM1 / インスリン抵抗 / 加齢/老化 / 内皮機能 / バイオマーカー |
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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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| 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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Report
(5 results)
Research Products
(49 results)
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[Journal Article] Establishment and characterization of a novel neuroendocrine carcinoma cell line derived from a human ascending colon tumor.2019
Author(s)
Shinji S, Sasaki N, Yamada T, Koizumi M, Matsuda A, Ohta R, Yokoyama Y, Takahashi G, Hotta M, Hara K, Takeda K, Ueda K, Kuriyama S, Ishiwata T, Murakami T, Ueda Y, Kanazawa Y, Yoshida H.
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Journal Title
Cancer Sci.
Volume: 110(12)
Issue: 12
Pages: 3708-3717
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Enhanced morphological and functional differences of pancreatic cancer with epithelial or mesenchymal characteristics in 3D culture.2019
Author(s)
Shichi Y, Sasaki N, Michishita M, Hasegawa F, Matsuda Y, Arai T, Gomi F, Aida J, Takubo K, Toyoda M, Yoshimura H, Takahashi K, Ishiwata T.
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Journal Title
Scientific Reports
Volume: 9
Issue: 1
Pages: 10871-10871
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] ABCG2-positive cells derived from ABCG2-negative pancreatic cancer cells in 3D-culture conditions show high stemness and anti-cancer drug resistance2018
Author(s)
Norihiko Sasaki, Fumio Hasegawa, Masaki Michishita, Yoko Matsuda, Tomio Arai, Naoshi Ishikawa, Yoko Itakura, Junko Aida, Kaiyo Takubo, Masashi Toyoda, Toshiyuki Ishiwata
Organizer
The American Association for Cancer Research Annual Meeting 2018
Related Report
Int'l Joint Research
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[Presentation] ABCG2-positive cells derived from ABCG2-negative pancreatic cancer cells in 3D-culture conditions show high stemness and anti-cancer drug resistance.2018
Author(s)
Norihiko Sasaki, Fumio Hasegawa, Masaki Michishita, Yoko Matsuda, Tomio Arai, Naoshi Ishikawa, Yoko Itakura, Junko Aida, Kaiyo Takubo, Masashi Toyoda, Toshiyuki Ishiwata
Organizer
The American Association for Cancer Research Annual Meeting 2018
Related Report
Int'l Joint Research
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