Mechanisms of morphology regulation in vascular endothelial cells
| Project/Area Number |
15K11259
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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 |
Surgical dentistry
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| Research Institution | Hokkaido University (2016-2018)
Kumamoto University (2015) |
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Principal Investigator |
Tamura Kiyomi 北海道大学, 歯学研究院, 助教 (90399973)
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| Project Period (FY) |
2015-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Keywords | 血管 / 血管新生 / 細胞伸長 / 血管内皮細胞 / ＥＳ細胞 / SM22 / ミオシン軽鎖 |
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| Outline of Final Research Achievements |
The earliest stage of formation of vascular structure requires proliferation, differentiation and morphological change in vascular endothelial cells. We focused on mechanisms of endothelial cell morphological change (cell elongation and formation of cord-like vessels). To examine signaling pathway regulating elongation of vascular endothelial cells, we performed a pharmacological screening method using vascular model of mouse ES cells. The inhibition of PI3K-Akt or mTORC1 caused elongation of vascular endothelial cells in the presence of a low concentration of VEGF, which usually does not induce endothelial cell elongation. In addition, our findings suggested that PI3K-Akt or mTORC1 differentially regulate endothelial cell elongation through transcription factor Foxo1-dependent or independent pathway, in response to the microenvironmental levels of VEGF.
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| Academic Significance and Societal Importance of the Research Achievements |
近年、再生医療による組織の回復が期待されているが、組織の再生には、その内部に酸素や栄養を供給する血管ネットワークが必要不可欠である。血管内皮細胞増殖因子（VEGF）等の増殖因子を用いた血管誘導が試みられているが、増殖因子の機能は、増殖・分化から形態調節まで多岐にわたるため、未成熟血管の過形成などの多くの問題がある。本研究の血管伸張を特異的に制御するメカニズムの解明によって、血管の形態形成過程についての基礎的理解が得られた。また、低濃度VEGF環境において血管伸張を誘導する化合物の同定は、VEGFの過剰投与を必要としない血管誘導方法の開発に貢献できると考えている。
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Report
(5 results)
Research Products
(16 results)
