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血管発達のFGF依存の代謝制御
Pengchun Yu1, Kerstin Wilhelm2, Alexandre Dubrac1
1Yale Cardiovascular Research Center, Yale University School of Medicine, New Haven, USA.
Nature
|May 4, 2017
まとめ
線維細胞成長因子 (FGF) 信号は,内皮細胞の代謝を制御することによって,血液とリンパ血管の発達を調節する. FGFのシグナル伝達は,細胞増殖と移動に不可欠なヘクソキナーゼ2 (HK2) を通じて糖分解を促進します.
科学分野:
- 血管生物学
- 細胞の代謝
- 分子信号
背景:
- 血液とリンパ系血管は 組織の酸素供給と 液体のバランスに不可欠です
- 内皮細胞の芽生え 移動 増殖は血管ネットワークの組み立ての鍵です
- 細胞代謝は血管の発達に著しく影響し,VEGFのシグナリングはよく研究されているが,FGFの役割はあまり理解されていない.
研究 の 目的:
- 血管の発達と代謝における線維細胞成長因子の役割を調査する.
- FGFシグナリングが内皮細胞機能に影響を与える分子メカニズムを解明する.
主な方法:
- 内皮細胞におけるFGF受容体 (FGFR) 信号伝達経路を研究した.
- c-MYC (MYC) とヘクソキナーゼ2 (HK2) 発現の調節を分析した.
- 使用されたノックアウトマウスモデル (パンエンドセリアおよびリンパ特異のHk2ノックアウト,Fgfr1/Fgfr3二重変異).
- FGF信号欠陥細胞に対するHK2過剰発現の影響を評価した.
主要な成果:
- FGFRのシグナリングは血管の発達を決定的に制御する.
- FGFシグナリングはMYC発現を制御し,MYCは HK2を制御する.
- HK2レベルが低下すると,内皮細胞の糖分解,増殖,移動が妨げられます.
- Fgfr1/Fgfr3変異体で見られたHk2ノックアウトフェノコピーの血管欠陥.
- HK2過剰発現は,FGFシグナル伝達による欠陥を部分的に救済する.
結論:
- FGFシグナル伝達は,内皮糖分解の重要なレギュラーである.
- このFGFに依存する代謝調節は,発達と成人の血管成長に不可欠です.
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