| Project/Area Number |
17K10769
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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 |
Cardiovascular surgery
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| Research Institution | Nippon Medical School |
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Principal Investigator |
JIRO KURITA 日本医科大学, 医学部, 病院講師 (20421183)
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| Co-Investigator(Kenkyū-buntansha) |
新田 隆 日本医科大学, 大学院医学研究科, 研究生 (40256954)
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| Project Period (FY) |
2017-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Fiscal Year 2019: ¥390,000 (Direct Cost: ¥300,000、Indirect Cost: ¥90,000)
Fiscal Year 2018: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | ずり応力 / シェアストレス / iPS細胞 / MARK経路 / ユビキチン / プロテアソーム / NF-κβ / ユビキチンプロテアソーム / 血管内皮細胞 / NF-κB / 血行力学 / 内皮細胞 |
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| Outline of Final Research Achievements |
Share stress is known to cause activation of NF-κβ. However the precise details of these phenomenon under different flow patterns are not well understood. So we studied the effect of disturbed flow versus pulsatile uniform flow as physiological types of blood flow on NF-κβ pathway. Our hypothesis are that respective flows have different effects on the degradation of Iκβα and the degradation induced by the ubiquitin-proteasome system(UPS).
In this study, we have shown that exposure to disturbed flow induced the degradation of Iκβα via UPS. Although the absolute level of phosphorylated Iκβα is unchanged, we see a relative increase in the phosphorylated rate of Iκβα. As a result, there is net activation of Iκβα. On the other hand, exposure to uniform flow somehow prevents Iκβα from the degradation in UPS pathway. Further studies are to be done to elucidate this novel mechanism of the degradation.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究では乱流がIκβαの分解を誘発し、Nf-κβを活性化させること。また、そのIκβαの分解はユビキチンプロテアソームシステム(UPS)によるものであると判明した。一方で、層流はYPSを介した分解を逃れて、NF-κβの不活性化に寄与していることも示した。今回、異なる血流パターンがNF-κβ経路に異なる影響を及ぼす実験結果を得た。しかし、これは血流が引き起こすごく一部の細胞応答反応を見ているにすぎない。今後もこのような血流が及ぼす動脈硬化機序の基礎的解明を継続し、外科手術における吻合部狭窄を予防する手段として、乱流を回避させる血行再建方法の開発や工夫についての基礎的知見の積み重ねを継続したい。
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