シリアー・ヘッジホッグ・シグナリング 損傷誘発性アディポゲネシス
Daniel Kopinke1, Elle C Roberson1, Jeremy F Reiter1
1Department of Biochemistry and Biophysics, Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA, USA.
Cell
|July 15, 2017
まとめ
骨格筋の再生は,年齢や筋縮による脂肪補充によって損なわれます. 脂肪の形成を防止し,筋肉の修復を促進する.
科学分野:
- 筋肉の再生と修復
- 細胞信号伝達経路
- アディポゲネシスと線維症
背景:
- 骨格筋の再生は年齢や筋縮によって衰え 脂肪の浸透を引き起こします
- 筋肉に宿る繊維/アディポジェニック原始体 (FAP) はアディポサイトに微分化し,脂肪の退化に寄与する.
- FAPのプライマリシリアは,ヘッジホッグ (Hh) のような細胞間信号を感知し,伝達するために不可欠です.
研究 の 目的:
- 骨格筋の再生と脂肪の退化におけるFAPのプライマリシリアの役割を調査する.
- FAPプライマリシリアによって制御される信号経路を決定する.
- 筋肉の脂肪補充を防ぐためにFAPの毛皮を標的とした治療戦略を探求する.
主な方法:
- FAPにおけるプライマリシリアの遺伝的消去
- 損傷後の筋肉再生とアディポゲネシスの分析とドゥシェンヌ筋縮症のマウスモデル.
- TIMP3とMMP14を含むHh信号経路の構成要素と下流ターゲットの調査
- TIMP3ミメティックを使用したFAPアディポゲネシスの薬理学的抑制.
主要な成果:
- 損傷とダッチェンヌ筋縮の両方のモデルで,FAPからシリアの遺伝的除去が阻害された.
- FAPのシリエーションを阻害すると,筋繊維の再生が強化され,筋繊維のサイズが減少しました.
- FAPシリア経由でのHhシグナル伝達はTIMP3発現を調節し,MMP14を阻害し,アディポゲネシスを阻害した.
- 薬学的なTIMP3ミメティックにより,FAPの脂肪細胞への変換が阻害されました.
結論:
- FAPによるシリアー・ヘッジホッグ信号は,骨格筋の再生反応の重要な調節因子です.
- FAPのプライマリシリアと関連したシグナル伝達経路をターゲットにすることで,骨格筋の脂肪退化を防ぐ潜在的な戦略が提供されます.
- FAPの生物学を理解することは,年齢に関連する筋肉の衰弱と筋縮の治療法の開発に不可欠です.
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