C/EBP同型タンパク質-10 (CHOP-10) は,内皮酸化窒素合成酵素の遺伝子発現を制御することにより,産後新血管化を制限する

Céline Loinard¹, Yasmine Zouggari, Patricia Rueda

¹Department of Medicine, Division of Cardiovascular Medicine, University of Cambridge, Addenbrooke’s Hospital, Cambridge, UK.

Circulation

|January 24, 2012

まとめ

C/EBPホモロゴスタンパク質10 (CHOP-10) は,産後新血管化を否定的に調節する. CHOP-10を削除すると,血管の形成と成熟が促進され,特に不血症や糖尿病の患者には効果があります.

科学分野:

分子生物学は分子生物学である.
心血管生物学心血管生物学
発達生物学発達生物学について

背景:

C/EBP同型タンパク質-10 (CHOP-10) は,細胞の分化,増殖,生存を調節する核タンパク質である.
産後新血管化におけるその役割は,ほとんど特徴づけられていなかった.

研究の目的:

産後新血管化のCHOP-10の機能を調査する.
血管形成におけるCHOP-10の役割の基礎となる分子メカニズムを解明する.

主な方法:

CHOP-10欠乏症のマウスモデル (CHOP-10(-/-)) と野生型の littermates を利用しました.
足関節動脈連動による誘発性性イシュケミア.
アンジオグラフィー,毛細血管密度測定,足のペルフュージョンを用いて新血管化を評価した.
研究されたアポトーシス,内皮酸化窒素合成酵素 (eNOS) 発現,およびeNOSプロモーターにCHOP-10結合.
人間の内皮細胞における短い干渉RNA (siRNA) と過剰発現の研究に従事した.

主要な成果:

CHOP-10の発現は,骨格筋の毛細血管で,イシュケミアと糖尿病の後に上昇調節された.
CHOP-10 (((-/-) マウスは,野生型のマウスと比較して,強化された新血管化,毛細血管の密度の増加,および改善された輸液を示した.
減少したアポトーシスと増加したeNOSレベルは,CHOP-10 (((-/-) マウスの缺血組織で観察されました.
CHOP-10はeNOSプロモーターに直接結合し,その転写活動を阻害する.
CHOP-10(-/-) のマウスのプロ血管新生効果は,CHOP-10/eNOSのダブルノックアウト動物では廃止された.
CHOP-10の糖尿病誘発のアップレギュレーションにより,後発血性新血管化が損なわれる.

結論:

CHOP-10は,産後新血管化の重要な負の調節剤として作用します.
CHOP-10は,部分的にeNOSの調節を通じて,容器の形成と成熟を調節します.
CHOP-10をターゲットにすることで,血管形成の障害を特徴とする疾患の治療の可能性が生まれます.

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