大细胞WEE1直接与NF-κB p65亚单元结合并酸化,诱导炎症反应并驱动动动脉硬化
Zhuqi Huang1,2,3, Sirui Shen4, Weixin Li1,4
1Department of Pharmacy and Institute of Inflammation, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, 310014, China.
Advanced science (Weinheim, Baden-Wurttemberg, Germany)
|April 9, 2025
概括
通过促进炎症,WEE1 G2检查点激酶 (WEE1) 驱动动动脉硬化. 在巨细胞中抑制WEE1可减少炎症并减轻动脉样硬化,确定WEE1作为治疗点.
科学领域:
- 心血管生物学 心血管生物学
- 分子医学是分子医学.
- 免疫学 免疫学 免疫学
背景情况:
- 动脉样硬化需要新的治疗点.
- 蛋白激酶调节动脉样硬化中的细胞过程.
- WEE1 G2检查点激酶 (WEE1) 与促进炎症有关.
研究的目的:
- 为了确定动脉样硬化症的新型治疗点.
- 研究WEE1在巨细胞介导炎症中的作用.
- 阐明WEE1影响动脉样硬化的机制.
主要方法:
- 激酶丰富分析和实验验证.
- RNA测序和突变WEE1等离子体研究.
- 在小鼠模型中对巨细胞特异的WEE1删除和药理抑制.
- 同免疫沉和蛋白质组学用于识别WEE1基质.
- 西部涂抹以确认酸化部位.
主要成果:
- 大细胞WEE1在S642的酸化与动脉样硬化相关.
- WEE1酸化,而不是表达,调解了oxLDL诱导的炎症.
- 大细胞WEE1的抑制减轻了小鼠的动脉样硬化.
- 在S536处,WEE1直接化NF-κB p65亚单元,增强炎症反应.
- 在p65激活过程中,WEE1起到上游激酶的作用.
结论:
- 巨细胞WEE1是通过NF-κB激活动脉样硬化的关键驱动因素.
- 准WEE1激酶活性为动脉样硬化提供了潜在的治疗策略.
- 确定WEE1是巨细胞中NF-κB信号传递的新型上游调节者.
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