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補足受容体C5aR1は,心臓再生の成功において進化的に保存された役割を果たす
Niranjana Natarajan1, Yamen Abbas1, Donald M Bryant1,2,3
1Department of Stem Cell and Regenerative Biology, Harvard Stem Cell Institute, Harvard University, Cambridge, MA (N.N., Y.A., D.M.B., A.U., L.H.C.-D., N.N.H., J.L.W., R.T.L.).
Circulation
|January 20, 2018
まとめ
種間の心臓再生の研究は,コンプリメント5a受容体1を活性化することで,心臓損傷後の心臓肌細胞の増殖を促進し,心臓の修復メカニズムに洞察を提供することを明らかにした.
科学分野:
- 心血管生物学
- 再生医療
- 比較ゲノミクス
背景:
- 成人哺乳類は 損傷後の心臓再生が限られている.
- 哺乳類の心臓修復の鍵となるのが 保存された分子経路の理解です
- 初期の再生のトランスクリプトミックの分析は 進化的に保存された経路を照らすことができます
研究 の 目的:
- 心臓再生のための 異種トランスクリプトミックのスクリーニングを 行うために
- 心臓の修復に関与する 保存された分子経路を特定するために
- 心筋細胞増殖における特定の免疫経路の役割を調査する.
主な方法:
- アクソロットル,新生児マウス,ゼブラフィッシュの心臓の傷害後のトランスクリプトミックの比較分析.
- アピカル切除 (10~20%の室内質量除去) 後の12,24,48時間のRNAシーケンシング
- 補完体5a受容体1 (C5aR1) の機能評価は,抑制と遺伝的消去を用いて行われます.
主要な成果:
- 補完受容体を含む炎症と補完経路の遺伝子のアップレギュレーションが保存されたことが種間で観察されました.
- 補足5α受容体1 (C5aR1) の発現が,再生中の心臓に誘発された.
- C5aR1の抑制または遺伝的消去は,心臓損傷後の心筋細胞増殖を著しく減少させた.
結論:
- コンプレメント5a受容体1の活性化は,心臓損傷後の心筋細胞増殖を促進する進化的に保存されたメカニズムである.
- コンプリメント経路の活性化は,心臓の再生に不可欠な共通経路です.
- コンプリメント経路をターゲットにすることで 心臓の修復が促進される可能性があります
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