滑动肌肉Notch1在血管损伤后调解了新阴位的形成
Yuxin Li1, Kyosuke Takeshita, Ping-Yen Liu
1Vascular Medicine Research, Brigham and Women's Hospital and Harvard Medical School, Cambridge, MA 02139, USA.
Circulation
|May 13, 2009
概括
血管光滑肌细胞中的Notch1信号驱动了受伤后的neointimal形成. 抑制Notch1显著减少了这一过程,这表明Notch1是血管增殖性疾病的治疗点.
科学领域:
- 心血管生物学 心血管生物学
- 细胞信号传递 细胞信号传递
- 血管生物学 血管生物学
背景情况:
- 诺奇1对细胞命运,血管生成和心血管发育至关重要.
- 它在产后血管损伤中的作用尚不清楚.
- 血管光滑肌细胞 (SMC) 中的Notch1信号可能会促进neointimal的形成.
研究的目的:
- 为了调查Notch1和Notch3在SMC中在血管损伤后的新极端形成期间的作用.
- 为了确定SMC中的Notch1缺陷是否会影响血管重塑.
主要方法:
- 野生型,诺奇1缺陷和诺奇3缺陷小鼠的动脉绑定.
- 评估新极端形成,SMC扩散,迁移和亡.
- 对Notch信号通路组件 (CHF1/Hey2) 的分析.
主要成果:
- 在受伤后,Notch1缺陷 (异合体,SMC特异性) 减少了70%的新终极形成.
- 诺奇3缺乏并没有影响新极端的形成.
- 缺少Notch1的SMCs表现出减少的增殖,迁移和增加的亡.
- 诺奇1信号通过CHF1/Hey2.2介导SMC的扩散和迁移.
结论:
- 诺奇1,而不是诺奇3,是SMC扩散和血管损伤后新极端形成的主要调解者.
- 在这种过程中,SMC中的Notch1/CHF1/Hey2路径至关重要.
- 在SMC中准Notch1/CHF1/Hey2可能为血管增殖性疾病提供治疗效益.
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The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not until 1985...
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