Elucidation of the cardiovascular network mechanism mediated by senescent vascular endothelial cell-derived factors
| Project/Area Number |
19K11759
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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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| Review Section |
Basic Section 59040:Nutrition science and health science-related
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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) |
2019-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2020: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Keywords | 内皮細胞 / 細胞老化 / へパラン硫酸脱硫酸化酵素 / 平滑筋細胞 / 形質転換 / ガングリオシド / 老化 / ラパマイシン / 血管内皮細胞 / ヘパラン硫酸脱硫酸化酵素 / 心血管 / 細胞間ネットワーク / 老化血管内皮細胞由来因子 |
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| Outline of Research at the Start |
血管内皮細胞の老化で分泌されるへパラン硫酸脱硫酸化酵素について、心血管系細胞への作用機序を明らかにするために、以下のような研究を計画している。
①血管内皮細胞に対する作用を明らかにするため、細胞老化誘導、内皮機能の変化、炎症刺激された内皮細胞の機能変化について検討する。
②心臓系細胞に対する作用を明らかにするため、平滑筋細胞、心臓線維芽細胞、心筋細胞の増殖性や機能変化について検討する。
③血中や組織での発現について検討する。
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| Outline of Final Research Achievements |
It was found that heparan sulfate desulfurizing enzyme 2 is not involved in the induction of cellular senescence. From in vivo analysis, it was found that heparan sulfate desulfurizing enzyme 2 is highly expressed in the aortic vascular endothelium of aged mice and the vascular endothelium of the heart, and is also increased in blood levels in aged mice. In order to proceed with in vivo analysis, we proceeded with the creation of vascular endothelium-specific knockout mice of heparan sulfate desulfurizing enzyme 2. Furthermore, it was found that the proportion of the main component of gangliosides, which is a group of glycolipids, increases during dedifferentiation in vascular smooth muscle cells, on which heparan sulfate desulfurizing enzyme 2 may act.
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| Academic Significance and Societal Importance of the Research Achievements |
生活習慣病の増加する中年層から高齢層にかけて生体内では老化細胞が蓄積し、動脈硬化を発端とする心血管疾患の発症、進展につながると考えられているが、詳しい分子メカニズムは不明である。今回の成果では、へパラン硫酸脱硫酸化酵素2がヒトの培養血管内皮細胞のみならず、マウス生体の加齢に伴って心血管および血中で増加すること、さらに血管の恒常性維持に働く平滑筋細胞の機能を制御する可能性が示された。今後さらにin vitroおよびin vivo研究をすすめることにより、へパラン硫酸脱硫酸化酵素2を標的とした心血管疾患を含む加齢性疾患の新たな治療法や予防法の開発につながると期待される。
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Report
(4 results)
Research Products
(60 results)
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[Journal Article] A New Anorectal Melanoma Cell Line Derived from a Primary Human Rectal Tumor2022
Author(s)
Shinji Seiichi、Shichi Yuuki、Yamada Takeshi、Takahashi Goro、Ohta Ryo、Sonoda Hiromichi、Matsuda Akihisa、Yonaga Kazuhide、Iwai Takuma、Takeda Kohki、Ueda Koji、Kuriyama Sho、Miyasaka Toshimitsu、Ueda Yoshibumi、Sasaki Norihiko、Takahashi Kimimasa、Ohashi Ryuji、Ishiwata Toshiyuki、Arai Tomio、Yoshida Hiroshi
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Journal Title
Journal of Nippon Medical School
Volume: 89
Issue: 4
Pages: 368-376
DOI
NAID
ISSN
1345-4676, 1347-3409
Year and Date
2022-08-25
Related Report
Peer Reviewed / Open Access
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[Journal Article] FGFR4 Inhibitor BLU9931 Attenuates Pancreatic Cancer Cell Proliferation and Invasion While Inducing Senescence: Evidence for Senolytic Therapy Potential in Pancreatic Cancer2020
Author(s)
Sasaki N, Gomi F, Yoshimura H, Yamamoto M, Matsuda Y, Michishita M, Hatakeyama H, Kawano Y, Toyoda M, Korc M, Ishiwata T.
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Journal Title
Cancers (Basel)
Volume: 12
Issue: 10
Pages: 2976-2976
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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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] TGF-beta1 induces epithelial-mesenchymal transition in the human colorectal neuroendocrine carcinoma cell line SS-22021
Author(s)
Seiichi Shinji, Norihiko Sasaki, Takeshi Yamada, Akihisa Matsuda, Ryo Ohta, Hiromichi Sonoda, Kazuhide Yonaga, Goro Takahashi, Takuma Iwai, Kohki Takeda, Koji Ueda, Sho Kuriyama, Toshimitsu Miyasaka, Fujiya Gomi, Toshiyuki Ishiwata, Hiroshi Yoshida
Organizer
第80回日本癌学会学術総会
Related Report
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[Presentation] Cellular senescence is additively induced in pancreatic cancer cell by FGFR4 inhibitor BLU99312021
Author(s)
Norihiko Sasaki, Fujiya Gomi, Hisashi Yoshimura, Masami Yamamoto, Yoko Matsuda, Masaki Michishita, Hitoshi Hatakeyama, Yoichi Kawano, Yoko Itakura, Masashi Toyoda, Murray Korc, Toshiyuki Ishiwata
Organizer
第80回日本癌学会学術総会
Related Report
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[Presentation] FGFR4シグナル抑制による膵癌の老化誘導と、老化細胞死誘導薬の有効性2021
Author(s)
佐々木紀彦, 五味不二也, 吉村久志, 山本昌美, 松田陽子, 道下正貴, 畠山仁, 川野陽一, 板倉陽子, 豊田雅士, マレーコーク, 石渡俊行
Organizer
第52回日本膵臓学会大会
Related Report
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[Presentation] FGFR4 inhibitor BLU9931 additively induces cellular senescence in pancreatic cancer cell for senolytic therapy2021
Author(s)
Norihiko Sasaki, Fujiya Gomi, Hisashi Yoshimura, Masami Yamamoto, Yoko Matsuda, Masaki Michishita, Hitoshi Hatakeyama, Yoichi Kawano, Yoko Itakura, Masashi Toyoda, Murray Korc, Toshiyuki Ishiwata
Organizer
The American Association for Cancer Research Annual Meeting 2021
Related Report
Int'l Joint Research
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[Presentation] Morphofunctional analysis of a novel neuroendocrine carcinoma cell line, SS-2 derived from a human ascending colon tumor2020
Author(s)
Seiichi Shinji, Norihiko Sasaki, Takeshi Yamada, Akihisa Matsuda, Ryo Ohta, Hiromichi Sonoda, Goro Takahashi, Takuma Iwai, Kohki Takeda, Koji Ueda, Sho Kuriyama, Toshimitsu Miyasaka, Fujiya Gomi, Toshiyuki Ishiwata, Hiroshi Yoshida
Organizer
第79回日本癌学会学術総会
Related Report
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[Presentation] A newly established neuroendocrine carcinoma cell line from a human ascending colon tumor shows high proliferation and CD133 expression in spherical cancer stem cell-like formation2020
Author(s)
Seiichi Shinji, Norihiko Sasaki, Takeshi Yamada, Michihiro Koizumi, Ryo Ohta, Akihisa Matsuda, Goro Takahashi, Masahiro Hotta, Takuma Iwai, Keisuke Hara, Kohki Takeda, Koji Ueda, Sho Kuriyama, Toshiyuki Ishiwata, Hiroshi Yoshida
Organizer
The American Association for Cancer Research Annual Meeting 2020
Related Report
Int'l Joint Research
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