FOXO1カップルの代謝活動と血管内皮の成長状態
Kerstin Wilhelm1, Katharina Happel1, Guy Eelen2,3
1Angiogenesis &Metabolism Laboratory, Max Planck Institute for Heart and Lung Research, D-61231 Bad Nauheim, Germany.
Nature
|January 7, 2016
まとめ
フォークヘッドボックスO (FOXO) 転写因子FOXO1は代謝を制御することによって内皮細胞の成長を調節する. FOXO1は内皮静止の門番として作用し,MYC信号を抑制して代謝活動を減速させ,血管拡張を制限する.
科学分野:
- 分子生物学
- 細胞生物学
- 血管生物学
背景:
- 内皮細胞 (ECs) は,異なる成長状態に適応する代謝の可塑性を示す.
- EC代謝と増殖を結びつける分子メカニズムを理解することは,血管の発達にとって極めて重要です.
研究 の 目的:
- フォークヘッドボックスO (FOXO) の転写因子FOXO1が,内皮細胞の代謝と血管の成長を調節する役割を調査する.
- FOXO1とMYCが内皮増殖と血管拡張を制御する分子ネットワークを解明する.
主な方法:
- FOXO1の内皮特異的欠損と過剰発現がマウスで確認された.
- EC増殖,移動,および血管形態の分析
- 糖分解とミトコンドリア呼吸の評価
- MYC信号経路の調査
主要な成果:
- FOXO1の内皮切除は,ECの増殖,増殖,血管拡大を引き起こした.
- FOXO1の強制的な発現は血管の成長を制限し,血管の薄れや細枝化を引き起こした.
- FOXO1はMYCシグナル伝達を抑制し,その結果,糖分解,ミトコンドリア呼吸,EC増殖を減少させます.
- MYC過剰発現は,EC代謝と血管の行動に対するFOXO1過剰発現の影響を逆転させた.
結論:
- FOXO1は血管成長の重要なレギュラーであり,内皮静止のゲートキーパーとして作用します.
- FOXO1-MYCの転写ネットワークは,内皮増殖と血管拡張を制御する新しい代謝チェックポイントとして機能する.
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