CD36调解了SARS-CoV-2包膜蛋白诱导的血小板激活和血栓形成
Zihan Tang1, Yanyan Xu2, Yun Tan3
1Department of Rheumatology and Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197 Ruijin Second Road, Shanghai, 200025, China.
Nature communications
|August 21, 2023
概括
严重的COVID-19与血液凝固问题有关. 研究人员发现,SARS-CoV-2包膜蛋白与CD36结合,激活血小板并引起血栓形成,提供了一个潜在的治疗点.
科学领域:
- 免疫学 免疫学 免疫学
- 病毒学 病毒学
- 血液学 血液学 血液学
背景情况:
- 异常凝血和血栓形成是严重COVID-19的标志.
- 驱动这些SARS-CoV-2感染后的血栓事件的确切机制尚未完全理解.
研究的目的:
- 阐明SARS-CoV-2包膜 (E) 蛋白在COVID-19相关的凝血障碍中的作用.
- 为了确定缓解E蛋白诱导血栓形成的分子标.
主要方法:
- 在COVID-19患者中测量血清SARS-CoV-2 E蛋白水平.
- 在小鼠的体内血栓形成模型中,使用E蛋白给药.
- 蛋白质拉下测试和质谱测试以确定E蛋白结合伙伴.
- 人类和小鼠模型中的血小板激活测定.
- 对CD36和p38MAPK通路的药理阻断和遗传缺陷研究.
主要成果:
- 血清E蛋白水平与COVID-19患者的凝血障碍相关.
- 静脉注射E蛋白诱导小鼠发生血栓形成.
- CD36 直接与SARS-CoV-2 E 蛋白结合.
- 与CD36结合的E蛋白通过p38 MAPK-NF-κB通路触发了血小板过活化.
- 抑制CD36或p38可显著降低E蛋白诱导的血小板激活和血栓形成在体外和体内.
结论:
- SARS-CoV-2 E 蛋白质在促进血小板过活和血栓形成方面发挥着关键作用.
- CD36-p38轴是E蛋白诱导的血小板激活的关键媒介.
- 准CD36-p38通路为管理COVID-19相关的血栓性并发症提供了潜在的治疗策略.
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