血管の滑らかな筋肉細胞移動におけるp27 (Kip1) の役割
1Cardiology Division, Center for Molecular Cardiology, Department of Medicine, Columbia University College of Physicians and Surgeons, Mount Sinai School of Medicine, New York, NY, USA.
Circulation
|June 20, 2001
まとめ
サイクリン依存キナーゼ阻害剤p27 (Kip1) は,ラパミシンが滑らかな筋肉細胞の移動を阻害する能力に不可欠です. その欠如はラパミシンの抗移動効果を大幅に低下させ,細胞の動きを調節する役割を強調します.
科学分野:
- 血管生物学 血管生物学
- 細胞シグナル伝達 細胞信号伝達
- 薬理学 薬理学とは
背景:
- ラパミシンは,滑らかな筋肉細胞 (SMC) の増殖と移動を抑制する.
- ラパミシンによるSMC増殖抑制には,p27(Kip1) のアップレギュレーションが含まれています.
- p27(Kip1) は,ラパマイシンの抗増殖効果に作用する.
研究 の 目的:
- SMCに対するラパミシンの抗移住効果を媒介するp27 (Kip1) の役割を調査する.
- SMC移動のラパミシン誘発阻害に p27 (Kip1) が不可欠であるかどうかを判断する.
主な方法:
- 改造されたボイドン室を用いて,野生型 (WT) とp27 ((Kip1)) の野生型 (WT) とp27 ((Kip1)) のp27 (Kip1)) のp27 (Kip1) のp27 (Kip1) のp27 (Kip1)) のp27 (Kip1) のp27 (Kip1)) のp27 (Kip1) のp27 (Kip1) のp27 (Kip1)) のp27 (Kip1)) のp27 (Kip1)) のp27 (Kip1)) のp27 (Kip1)) のp27 (Kip1)) のp27 (Kip1) (Kip1)) のp27 (Kip1)) のp27 (Kip1)) のp27 (Kip1) (Kip1)) のp27 (Kip1) (Kip1)) のp27 (Kip1) (Kip1)) のp27 (Kip1) (Kip1)) のp27 (Kip1)) のp27 (Kip1) (Kip1)) のp27 (p27 (Kip1)) のp27 (p27 (Kip1)) のp27 (p27Kip1)) のp27 (p27 (p27Kip1)) のp27 (p27Kip1)) のp27 (p27 (p27Kip1)) のp27 (p27Kip1)
- WT,p27(+/-),およびp27(-/-) のマウスにおける大動脈SMCの爆発的移住に対するラパミシンの影響を評価.
主要な成果:
- ラパミシンの用量依存性により,WT SMC 移行は抑制されましたが,p27(Kip1)((-/-) SMC 移行は抑制されていません.
- システミックなラパミシンの投与は,WTとp27のマウスのSMC移動を90%大幅に抑制しました.
- p27 ((Kip1) ((-/-) マウスは,ラパミシンに対する反応として,SMCの移動を有意に抑制しなかった.
結論:
- p27 (Kip1) の欠如は,ラパミシンのSMC移動に対する抑制効果を低下させる.
- p27(Kip1) は,SMCの移行を制御するシグナル伝達経路に関与しています.
- p27 (Kip1) は,ラパミシンの滑らかな筋肉細胞に対する抗移動作用の重要な媒介である.
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