シヌソイド内皮からの誘導性血管新生信号は,肝臓の再生に必要なものです
Bi-Sen Ding1, Daniel J Nolan, Jason M Butler
1Howard Hughes Medical Institute, Ansary Stem Cell Institute, and Department of Genetic Medicine, Weill Cornell Medical College, New York, New York 10065, USA.
Nature
|November 12, 2010
まとめ
肝臓のシヌソイド内皮細胞 (LSEC) は,肝臓細胞の増殖を刺激する血管新生因子を放出することによって,肝臓の再生を開始します. VEGFR2-Id1シグナル伝達によって媒介されるこのプロセスは,損傷後の肝臓の質量の回復に不可欠です.
科学分野:
- 血管生物学 血管生物学
- 肝臓病理学 肝臓病理学
- 再生医学は,再生医療である.
背景:
- 内皮細胞は,指示的な血管のニッチを確立することによって,オルガノゲネシスと再生において重要な役割を果たします.
- 内皮細胞によって分泌される血管新生因子は,血液形成における役割と同様に,組織修復と再生をサポートします.
- 特定の内皮細胞が成人の臓器再生を促進する正確なメカニズムは,依然としてほとんど不明です.
研究 の 目的:
- 部分肝切除術後の肝臓内皮内皮細胞 (LSECs) が肝臓再生を開始し,維持するメカニズムを解明する.
- 特定の分子経路とLSEC媒介性肝臓再生に関与する要因を特定する.
- 肝臓再生を促進するLSECの治療的可能性を調査する.
主な方法:
- ネズミの70%部分肝切除モデルを使用して,生理学的肝臓再生を研究しました.
- LSECにおける血管内皮成長因子受容体-2 (VEGFR2) と転写因子Id1の役割を調査した.
- 誘導可能な遺伝子アブレーション,インビトロ共同培養,およびLSECの内移植を使用した.
主要な成果:
- LSECsは,VEGFR3 ((+) CD34 ((-) VEGFR2 (((+) VE-cadherin (((+) FactorVIII (((+) CD45 ((-)) として定義され,血管新生因子を介して肝臓の再生を開始します.
- LSECsにおけるVEGFR2の遺伝的アブレーションは,Id1のアップレギュレーションを阻害することによって,肝細胞の増殖と肝臓質量の再構成を阻害しました.
- LSECにおけるId1欠乏は,肝臓再生を阻害する主要な血管新生因子 (HGF,Wnt2) の発現を低下させる.
- 実験室内および実験室内での研究では,LSECにおけるVEGFR2-Id1の活性化が肝細胞の増殖と再生を刺激することを示しました.
結論:
- LSECにおけるVEGFR2-Id1媒介のシグナリングは,誘導性血管新生と血管新生因子 (Wnt2,HGF) の放出を通じて肝臓の再生を開始するために不可欠です.
- LSECによるVEGFR2-Id1依存の増殖性血管新生は,損傷後の肝臓の質量を復元します.
- エンジニアリングされたLSECと肝細胞の治療的共同移植は,持続的な肝臓再生のための有望な戦略を提供します.
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