内皮由来のハイパーポラライジングファクター媒介のリラクゼーションにおけるケベオラー区画の役割:Ca2+信号とギャップジャンクション機能は,内皮細胞のケベオリンによって調節される

J Saliez¹, C Bouzin, G Rath

¹Unit of Pharmacology and Therapeutics, Université catholique de Louvain, Medical School, Brussels, Belgium.

Circulation

|February 13, 2008

まとめ

カヴェオリン-1は,内皮由来高極化因子 (EDHF) 媒介によるリラックスに不可欠です. 欠乏すると,血管の膨張に不可欠なカルシウムチャネルとギャップジャンクションが損なわれます.

科学分野:

血管生物学血管生物学
内皮細胞生理学内皮細胞生理学
分子医学は分子医学である.

背景:

洞窟の構造タンパク質であるカヴェオリン-1は,シグナリング分子を支度し,内皮細胞のタンパク質活動を調節する.
カリウムチャネルとコネクシン43を含む,内皮由来の高極化因子 (EDHF) 媒介によるリラックスにおける主要な媒介者は,カベオラで発見され,またはカベオリン-1によって調節される.

研究の目的:

EDHF媒介の血管リラクゼーションにおけるカベオリン-1の役割を調査する.
カヴェオリン-1欠乏が内皮細胞機能,カルシウムホメオスタシス,ギャップ・ジャンクション・コミュニケーションに与える影響を決定する.

主な方法:

カヴェオリン-1ノックアウトと野生型のマウスのメゼンテリック動脈の比較分析.
血管拡張,カルシウムホメオスタシス,TRPV4チャネルの活性に関する評価.
ギャップ・ジャンクションとコネクシン発現の形態学的および分子的特徴.

主要な成果:

カベオリン-1ノックアウトマウスは,EDHF媒介の血管拡張の完全な欠如を示した.
カルシウムホメオスタシスの障害とTRPV4カチオンチャネルの活性低下は,カヴェオリン-1が欠けている内皮細胞で観察されました.
コネクシン37,40,43の発現が低下すると,ギャップ・ジャンクションが少なくなり,ノックアウト動脈における筋内皮細胞の伝達が変化する.
TRPV4チャネルとコネクシンが,プラズマ膜の洞窟分泌区内のカヴェオリン-1とコロカライズすることが判明しました.

結論:

カベオリン-1発現は,EDHFに関連するリラックスに不可欠です.
Caveolin-1は,EDHFシグナル伝達経路の重要な構成要素であるTRPV4チャネルとコネクシンの膜局部化と活性を調節する.

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