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CXCL12/プロテオグリカン相互作用の選択的遺伝的無効性を有するマウスのホメオスタティックおよび組織修復のデフォルト
Patricia Rueda1, Adèle Richart, Alice Récalde
1Institut Pasteur, Unité de Pathogénie Virale, Département de Virologie, INSERM U819, Paris, France.
Circulation
|October 5, 2012
まとめ
CXCL12のようなケモカインは,細胞シグナル伝達のために,硫酸ヘパラン経由で不動化する. この相互作用を妨害すると,再血管化は損なわれ,組織修復とケモカイン機能における重要な役割が証明される.
科学分野:
- 免疫学 免疫学とは
- 細胞生物学 細胞生物学
- バイオケミストリー バイオケミストリー
背景:
- ケモカインは,硫酸ヘパランプロテオグリカンと相互作用して,細胞表面と細胞外マトリックスに固定されます.
- この相互作用は細胞の指向とシグナル伝達に不可欠ですが,そのインビボの結果は完全に理解されていません.
研究 の 目的:
- 固有のケモカイン機能におけるヘパラン硫酸塩の相互作用の役割を in vivo で調査する.
- 生理学的および病理学的プロセスに障害のあるケモカイン不動化の影響を理解する.
主な方法:
- マウスモデル (Cxcl12(Gagtm)) を設計し,ヘパラン硫酸の結合を防止する突然変異を起こしたが,CXCR4のシグナル伝達を維持した.
- 分析されたCxcl12 (((Gagtm/Gagtm) のマウスは,正常な発達,造血前駆細胞数,および誘発された急性性イシュケミアへの反応を測定した.
- 変異性CXCL12γとその変異体を外来的に投与し,変異性マウスの再血管化能力を評価した.
主要な成果:
- Cxcl12 (((Gagtm/Gagtm) のマウスは正常な発達と循環中のCD34 (((+) 細胞の増加を示した.
- 高CXCL12発現にもかかわらず,変異性マウスの不血性組織では,再血管化の障害と細胞浸透の減少が観察されました.
- 外因的なCXCL12γは血管の成長を回復させ,非結合性突然変異体はそうすることができなかった.
結論:
- ヘパラン硫酸の相互作用は,ホメオスタシスと疾患におけるCXCL12の機能に不可欠です.
- ケモカイン固定化のインビボパラダイムを初めて実証した.
- ケモカイン-ヘパラン硫酸塩相互作用を標的とした治療の可能性を強調しています.
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