剪切诱导的CCN1促进了甲状腺内皮表型和动脉样硬化
Pei-Ling Hsu1,2, Jheng-Sin Chen1, Chin-Yung Wang1
1Department of Cell Biology and Anatomy (P.-L.H., J.-S.C., C.-Y.W., F.-E M.), College of Medicine, National Cheng Kung University, Tainan, Taiwan.
Circulation
|March 29, 2019
概括
通过激活内皮细胞中的核因子-κB,母细胞蛋白CCN1促进动脉样硬化. 阻断CCN1-整合素α6β1与T1的结合抑制了这一过程,为动脉样硬化提供了潜在的治疗策略.
科学领域:
- 心血管生物学
- 分子医学
- 细胞生物学
背景情况:
- 动脉样硬化的发展与血管血流障碍有关.
- 通过干扰流动和动脉硬化病变在内皮细胞中升高调节的母细胞蛋白CCN1.
- CCN1在动脉样硬化的具体作用尚不清楚.
研究的目的:
- 在动脉样硬化中研究CCN1的体内和体外功能.
- 阐明CCN1在流动条件下影响内皮细胞行为的分子机制.
主要方法:
- 为研究CCN1在动脉样硬化中的作用,生成了试验小鼠 (Ccn1-dm/Apoe-/).
- 在实验室中使用了在层流和振荡流下对内皮细胞 (人类和小鼠) 的剪切应力实验.
- 评估了斑块形成,氧化应激,炎症标志物和核因子-κB (NF-κB) 激活.
主要成果:
- 在动脉绑定后,动脉硬化病变的进展增加了CCN1表达.
- 与对照小鼠相比,Ccn1-dm/Apoe-/小鼠对动脉样硬化的显著抵抗.
- 在Ccn1-dm/Apoe-/小鼠中观察到氧化应激降低,炎症标志物和单细胞回归.
- 通过CCN1/α6β1信号传导流动诱导的NF-κB激活,促进阿瑟罗基因表达.
- 发现了CCN1/α6β1和NF-κB之间的正反循环,该循环因Ccn1-dm突变或T1而被破坏.
结论:
- 通过调节内皮细胞表型,CCN1在动脉样硬化中起作用.
- CCN1与整合素α6β1结合,激活NF-κB,从而创建一个自我延续的循环,驱动动脉动生成.
- 针对CCN1-α6β1相互作用的T1显示出开发新型动脉样硬化疗法的潜力.
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