Opposing actions of Notch1 and VEGF in post-natal cardiac valve endothelial cells.
Opposing actions of Notch1 and VEGF in post-natal cardiac valve endothelial cells.
复制标题
Notch1 和 VEGF 在出生后心脏瓣膜内皮细胞中的相反作用。
DOI：
10.1016/j.bbrc.2008.07.057
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发表时间：
2008
影响因子：
3.1
通讯作者：
Bischoff,Joyce
中科院分区：
文献类型：
--
作者：
Yang,Jeong-Hee;Wylie-Sears,Jill;Bischoff,Joyce
与其他血管系统相比，心脏瓣膜的内皮细胞在体外对转化生长因子-β (TGF-β)的响应中进行内皮到间充质转化（EMT）的能力是独一无二的。EMT是胚胎瓣膜发育过程中的一个关键事件，VEGF-A和Notch1都被证明在这一过程中起作用。在这里，我们研究了VEGF-A和Notch1对成人主动脉瓣小叶克隆内皮细胞（EC）群体EMT的影响。VEGF-A抑制TGF-β诱导的EMT。然而，内皮细胞生长不受VEGF-A或TGF-β的影响。三个实验揭示了Notch1的积极作用：(1)TGF-β诱导瓣膜ECs中的Notch1 mRNA， (2) Notch1信号的γ分泌酶抑制剂阻断EMT， (3) Notch1配体非依赖性形式的过表达诱导EMT。这些结果首次表明，VEGF-A和Notch1在调节出生后瓣膜内皮的EMT中发挥相反的作用。
The endothelium of the cardiac valves is unique compared the rest of the vasculature in its ability to undergo an endothelial-to-mesenchymal transformation (EMT) in vitro in response to transforming growth factor-β (TGF-β). EMT is a critical event during embryonic valve development, and both VEGF-A and Notch1 have been shown to function in this process. Here we investigate the effects of VEGF-A and Notch1 on EMT in clonal endothelial cell (EC) populations isolated from adult aortic valve leaflets. VEGF-A inhibited TGF-β-induced EMT. Endothelial growth, however, was not affected by VEGF-A or TGF-β. A positive role for Notch1 was revealed in three experiments: (1) TGF-β induced Notch1 mRNA in valve ECs, (2) a γ-secretase inhibitor of Notch1 signaling blocked EMT, and (3) overexpression of a ligand-independent form of Notch1 induced EMT. These results demonstrate, for the first time, that VEGF-A and Notch1 play opposing roles in regulating EMT in post-natal valve endothelium.