通过激活痕信号通路,减少内皮细胞中VE-卡德林的表达
Yuanqing Zhang1,2,3, Jie Wang4, Tianran Huai2,3
1Department of Respiratory and Intensive Care Unit, The First Affiliated Hospital of Shandong First Medical University and Shandong Provincial Qianfoshan Hospital, Shandong Institute of Respiratory Diseases, Jinan, China.
Journal of biochemical and molecular toxicology
|January 12, 2025
概括
暴露激活了Notch信号通路,降低了内皮细胞中的VE-cadherin表达,并增加了血管透性. 这项研究阐明了引起的血管功能障碍的一个关键机制.
科学领域:
- 毒理学 毒理学 毒理学
- 血管生物学 血管生物学
- 细胞信号传递 细胞信号传递
背景情况:
- (Cd) 是一种有毒的重金属,与血管疾病有关.
- 疾病会影响血管内皮细胞 (ECs),但分子机制尚不清楚.
- 缺口信号通路的破坏与EC功能障碍有关.
研究的目的:
- 研究低度对ECs中Notch信号通路的影响.
- 确定Cd对VE-cadherin表达和EC透性的影响.
- 阐明Notch信号在Cd诱导的血管变化中的作用.
主要方法:
- 用低剂量Cd (2.28 mg/kg) 治疗的小鼠,以分析大脑和脏组织中的Notch途径组件和VE-cadherin.
- 在体外研究中,使用人静脉内皮细胞 (HUVEC) 接触低Cd度 (1μM).
- 评估了诺奇通路元素 (NICD1,Hes1,Hey1,Hey2) 和VE-cadherin的mRNA和蛋白质水平.
- 测量了HUVEC的透性,并使用DAPT,一种Notch抑制剂来评估其作用.
主要成果:
- 暴露于Cd增加了NICD1,Hes1,Hey1和Hey2的表达,同时降低了小鼠组织和HUVEC中的VE-cadherin.
- 低Cd度增加了HUVEC的透性.
- 发现痕信号可以负面调节VE-cadherin的表达.
- DAPT治疗逆转了Cd诱导的VE-cadherin表达的减少.
结论:
- 暴露于会激活内皮细胞中的Notch信号通路.
- 这种激活导致VE-cadherin表达的减少和血管透性的增加.
- 这些发现揭示了Cd通过Notch信号诱导血管损伤的新机制,突出了潜在的治疗点.
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