TBX20はプロキネチシン2-プロキネチシン受容体1経路を通じて血管新生を調節する
Shu Meng1, Qilin Gu1, Xiaojie Yang1
1Center for Cardiovascular Regeneration, Department of Cardiovascular Sciences, Houston Methodist Research Institute, TX.
Circulation
|March 17, 2018
まとめ
TBX20は,PROK2-PROKR1経路を通じて血管新生を調節する新しい転写因子です. この発見は 異常な血管形成を伴う疾患の 新しい治療目標を提供します
科学分野:
- 心血管生物学
- 分子生物学
- 発達生物学
背景:
- 血管新生は胚の発達と病理学にとって不可欠です
- 転写因子であるTBX20は胚の発達に不可欠であり,先天性心疾患と関連しています.
- 血管新生におけるTBX20の特定の役割は未明でした.
研究 の 目的:
- 血管新生を調節する TBX20 の役割を調査する.
- 血管新生に関わるTBX20のダウンストリーム標的を特定する.
- TBX20-血管新生経路の 治療の可能性を探るため
主な方法:
- 血管新生 (in vitro と in vivo) で TBX20 を研究するために,機能喪失と機能獲得のアプローチを使用した.
- 血管新生遺伝子配列を用いて TBX20の下流標的を特定した
- 遺伝子ノックダウンと救出実験を含む,マウスモデルとゼブラフィッシュで検証された結果.
主要な成果:
- TBX20のノックダウンにより,プロキネチシン2 (PROK2) 発現が著しく低下し,内皮細胞の移動とインビトロ血管新生が低下した.
- TBX20欠乏症は,ネズミのモデルでPROK2発現とプラグ内血管新生を減少させた.
- PROK2の投与により血管新生と血流回復が促進され,tbx20およびprok2 / prok1aの破壊によりゼブラフィッシュの血管新生が阻害され,prok2 / prok1aの過剰発現により回復が観察されました.
結論:
- PROK2-PROKR1経路を通じた血管新生の新しいレギュレータとして TBX20を特定しました.
- 血管内皮成長因子の 血管新生効果を維持する TBX20-PROK2-PROKR1 信号カスケードを明らかにした.
- この経路は血管新生関連の疾患の 潜在的な治療目標として提案されました
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