ETS2 と NFAT リンクの協力結合 Erk1/2 とカルシヌーリンのシグナル伝達が心臓縮の病原性である
Yuxuan Luo1, Nan Jiang1, Herman I May1
1Departments of Internal Medicine, Cardiology Division (Y.L., N.J., H.I.M., X.L., A.F., G.G.S., G.C., Q.L., C.L., B.A.R., S.L., T.G.G., J.A.H.), University of Texas Southwestern Medical Center, Dallas.
Circulation
|April 6, 2021
まとめ
ERK1/ 2によるETS2の活性化は,心筋縮に極めて重要です. この研究では,ETS2がNFATと複合体を形成し,マイクロRNA-223を新型のプロハイパートロフィック標的として特定し,心不全メカニズムの理解を進めています.
科学分野:
- 心血管生物学
- 分子心臓科
- 遺伝子規制
背景:
- 心臓膨張は 心不全の主要な危険因子であり,世界的に主要な死因です.
- カルシヌーリン/ NFATとMAPK/ ERK経路は,心筋縮の病原性に関与しています.
- これらの経路とNFATの目標の間の正確な相互作用は,まだ完全に理解されていません.
研究 の 目的:
- ETS2が心筋縮における役割を調査する.
- ETS2と心筋縮経路を結びつける分子メカニズムを解明する.
主な方法:
- 心筋細胞特異的な ETS2 ノックアウトマウスの生成
- 主要心筋細胞におけるETS2機能の評価
- 心臓組織における遺伝子発現とタンパク質の相互作用の分析
主要な成果:
- ETS2は,ヒトとマウスの心臓における高縮刺激への反応として,Erk1/ 2によって活性化されます.
- ETS2欠乏症は,圧力の過剰に起因する心筋縮から保護します.
- ETS2はNFATと相互作用し,microRNA-223を含む高縮性遺伝子の転写を促進する.
- マイクロRNA-223抑制はカルシヌーリン媒介性心筋縮を抑制する.
結論:
- ETS2はカルシヌーリン/ NFAT経路による心筋縮において重要な役割を果たします.
- ETS2のErk1/2活性化とNFAT/ETS2標的遺伝子発現の間に新しい分子リンクが確立された.
- マイクロRNA-223は,心筋縮における新たなプロハイパートロフィック標的として特定されています.
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