巨细胞衍生的外体体miR-146a-5p调节PNKP/DDOST/JAGN1复合体,以调节动脉样硬化中NETs的形成
Zhen Liu1, Wei Zhang1, Yihang Li1
1Department of Vascular Surgery, First Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan 450052, China.
Cellular signalling
|October 18, 2025
概括
携带miR-146a-5p的巨细胞外体细胞通过PNKP/DDOST/JAGN1通路调节中性粒细胞外细胞陷 (NET) 的形成,为动脉样硬化 (AS) 提供新的治疗点. 这一发现揭示了AS进展中的巨细胞-中性粒细胞相互作用.
科学领域:
- 分子生物学分子生物学
- 免疫学 免疫学 免疫学
- 心血管研究研究心血管研究
背景情况:
- 动脉样硬化 (AS) 的进展与中性粒细胞外细胞陷 (NET) 的形成有关.
- 在AS中,巨细胞和中性粒细胞之间的精确调节相互作用仍然不完全理解.
研究的目的:
- 阐明巨细胞衍生的外体在调节动脉样硬化期间的NET形成中的作用.
- 研究涉及miR-146a-5p及其下游目标的特定分子机制.
主要方法:
- 在ApoE-/-小鼠中建立了动脉样硬化模型.
- 从氧化低密度脂蛋白 (ox-LDL) 刺激的巨细胞中分离出来的外体.
- 使用qRT-PCR,西斑,共免疫沉,RIP和双化酶记者测试对PNKP/DDOST/JAGN1复合物的miR-146a-5p调节进行分析.
主要成果:
- 巨细胞衍生的外体显示了miR-146a-5p的增加,抑制PNKP和改变DDOST酸化.
- 这个级联激活了JAGN1依赖的NET形成.
- 在AS小鼠中,抑制miR-146a-5p降低了NETs,活性氧物种 (ROS),斑块负担和炎症.
结论:
- 巨细胞外体miR-146a-5p通过PNKP/DDOST/JAGN1轴调节NET的形成.
- 这一途径在AS病变发生过程中呈现出一种新的机制.
- 确定了AS治疗的潜在治疗点.
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