内皮由来の血管新生信号は,再生性肺アルベオライゼーションを誘発し,維持する

Bi-Sen Ding¹, Daniel J Nolan, Peipei Guo

¹Ansary Stem Cell Institute, Department of Genetic Medicine, Weill Cornell Medical College, New York, NY 10065, USA.

Cell

|November 1, 2011

まとめ

大人の肺再生には,肺毛細血管内皮細胞 (PCEC) が関与し,上皮原細胞の増殖を刺激する成長因子を産生します. このプロセスは,肺損傷後のアルヴェオロゲネシスにとって極めて重要です.

科学分野:

肺内医学は肺内医学である.
再生生物学再生生物学とは
細胞生物学細胞生物学

背景:

大人の肺の再生は,細胞の反応を調整した複雑なプロセスです.
片側肺切除術 (PNX) は,残りの肺組織における再生性アルベオライゼーションを研究するために使用されるモデルです.

研究の目的:

大人の肺再生を促す重要な分子経路と細胞相互作用を特定する.
肺毛細血管内皮細胞 (PCEC) とその分泌する因子のアルヴェオゲネシスにおける役割を明らかにする.

主な方法:

片側肺切除術 (PNX) のマウスモデルを使用した.
VEGFR2とFGFR1.1の内皮特異的誘導性遺伝子アブレーションを採用しています.
MMP14の機能とEGFRシグナル伝達との相互作用を研究した.

主要な成果:

PNXはPCECを刺激して,上皮原始細胞の増殖とアルベオゲネシスを促進する血管新生因子を産生させます.
内皮細胞におけるVegfr2およびFgfr1の遺伝的アブレーションにより,MMP14の産生およびその後のアルベオライゼーションが低下した.
MMP14は,上皮細胞の膨張に不可欠なEGFのようなエクトドメインを明らかにすることによって,EGFRシグナリングを活性化することが示されました.

結論:

PCECにおけるVEGFR2およびFGFR1の活性化は,MMP14に依存するEGFRリガンドの生物利用性を駆動し,アルベオゲネシスを開始および維持します.
この経路をターゲットにすることが,肺再生における治療的介入の可能性を秘めている.
EGFの投与またはMMP14(+) PCECの移植で肺機能の回復が観察されました.

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