心臓の再生能力のホルモン制御の証拠
Kentaro Hirose1,2, Alexander Y Payumo1,2, Stephen Cutie1,2
1Cardiovascular Research Institute and Department of Physiology, University of California, San Francisco, San Francisco, CA 94158, USA.
まとめ
哺乳類の心臓の再生は 甲状腺ホルモンの増加により失われ エンドサーミーの代償となります この研究は,甲状腺ホルモンのシグナル伝達と心筋細胞サイクル停止と,成人哺乳類の再生能力の低下を関連付けています.
科学分野:
- 比較生物学
- 生理学
- 発達生物学
背景:
- 組織再生の可能性は種と発達段階によって大きく異なるが,そのメカニズムは十分に理解されていない.
- 哺乳類の心臓再生は成人では顕著に欠けていて,心筋細胞循環停止とポリプロイド化と相関しています.
- 哺乳類の内熱性 (熱血性) の進化は,この再生能力の喪失と一致する.
研究 の 目的:
- 成人哺乳類の心臓再生能力の喪失の根本的なメカニズムを調査する.
- 代謝率,体温,甲状腺ホルモン,心筋細胞増殖の関係を調べる
- 甲状腺ホルモンのシグナル伝達が 心臓再生を制御する役割を 決定する
主な方法:
- 代謝率,体温,血清チロキシン値と相関した 41種の二倍体心肌細胞の豊富さを分析した.
- 成人マウスにおける甲状腺ホルモンのシグナル伝達を不活性化させることで,心筋細胞のポリプロイド化と細胞サイクル終了への影響を研究した.
- 生体外甲状腺ホルモンが 回復力のある種であるゼブラフィッシュの心臓再生に及ぼす影響を調べました
主要な成果:
- 二倍体心筋細胞の豊富さは,クレイバーの法則 (3/4の法則スケーリング) に従い,代謝率,体温,甲状腺素レベルと逆相関しています.
- 成人マウスでは,甲状腺ホルモンのシグナル伝達が低下し,心筋細胞のポリプロイド化が低下し,細胞周期の退出が遅れて,心臓の再生能力が保たれた.
- ゼブラフィッシュに甲状腺ホルモンを投与すると 心臓再生能力が低下します
結論:
- 成人哺乳類の心臓再生能力の喪失は,甲状腺ホルモンのレベルが上昇したことで引き起こされるようです.
- 哺乳類における内熱の獲得は,甲状腺ホルモンが媒介する心臓の再生能力とのトレードオフを伴う可能性があります.
- 甲状腺ホルモンのシグナル伝達は,心筋細胞の細胞サイクル進行と心臓再生の重要な調節因子です.
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