アポプトティック細胞から放出された代謝物は,組織伝達物質として作用する
Christopher B Medina1,2, Parul Mehrotra3, Sanja Arandjelovic1,2
1Center for Cell Clearance, University of Virginia, Charlottesville, VA, USA.
Nature
|April 3, 2020
まとめ
アポプトティック細胞は,隣接する細胞にシグナルを送るため,被動的にではなく,積極的に特定の代謝産物を放出します. これは規制された
科学分野:
- 細胞生物学
- 免疫学
- メタボロミクス
背景:
- カスパースに依存したアポトーシスは,組織ホメオスタシス,炎症,増殖,再生を調節するために不可欠です.
- アポプトティック細胞が組織環境に様々な影響を及ぼす正確なメカニズムは,まだ完全に理解されていません.
研究 の 目的:
- アポプトティック細胞のメタボリート分泌をプロファイルする.
- これらの放出された代謝産物の 隣接する細胞と疾患モデルの 機能的影響を調査する.
主な方法:
- 各種の細胞から分泌されるアポプトシス代謝物のプロファイリング.
- メタボリート放出におけるカスパーゼ媒介パネキシン1チャネルの役割を調査する.
- 健康な細胞の遺伝子発現に対するアポプトシス分泌体の影響を評価する.
- 炎症性関節炎と肺移植拒絶のマウスモデルにおけるアポプトシス代謝物の治療的可能性を評価する.
主要な成果:
- アポプトティック細胞は,膜の完全性を維持しながら,特定の,調節された代謝産物のサブセットを放出します.
- メタボリットの放出は,継続的な代謝活動とともに,カスペーゼ媒介パネキシン1チャネル開通によって促進されます.
- アポプトシスシクレトームは炎症や細胞増殖を抑制し,受容細胞の創傷治癒を促進します.
- 炎症性関節炎と肺移植の拒絶モデルでは,アポプトシス代謝産物のカクテルが疾患の重症度を有意に低下させた.
結論:
- アポプトシス細胞は"アポプトシスシクレトーム"と呼ばれるメタボリートの制御された放出によって周囲と活発にコミュニケーションをとる.
- このセクレトームは"さよなら"信号として機能し,解消とホメオスタシスを促進するために組織反応を積極的に調節します.
- これらの発見は,アポプトシス細胞の役割を,受動的存在から組織微小環境と疾患のアウトカムを活性化するものに再定義します.
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