烟雾和尖:本佐[a]皮林通过促进NR4A2诱导的ACE2和TMPRSS2表达来增强SARS-CoV-2感染
Wenbin Liu1,2,3, Yue Zhao1,2,3, Junyan Fan1,2,3
1Key Laboratory of Biosafety Defense, Ministry of Education, Shanghai, 200433, China.
Advanced science (Weinheim, Baden-Wurttemberg, Germany)
|July 10, 2023
概括
香烟烟雾中含有的酸 (benzo[a]pyrene) 通过增加ACE2和TMPRSS2.2,使SARS-CoV-2感染恶化. 这种机制涉及NR4A2上调,突出显示了COVID-19的吸烟风险,特别是在老年人中.
科学领域:
- 分子生物学分子生物学
- 病毒学 病毒学
- 毒理学 毒理学 毒理学
背景情况:
- 香烟烟雾加剧了SARS-CoV-2感染,但机制尚不清楚.
- 香烟烟雾中的关键成分[a]皮林 (benzo[a]pyrene) 与病毒病原发生有关.
研究的目的:
- 阐明佐[a]烯促进SARS-CoV-2感染的分子机制.
- 调查核受体子家族4A号2 (NR4A2) 在这个过程中的作用.
主要方法:
- 研究了[a]皮林对肺细胞和有机体中ACE2和TMPRSS2表达的作用.
- 使用了SARS-CoV-2伪病毒和真实的Omicron BA.5.5.
- 检查了NR4A2与ACE2和TMPRSS2促进体的结合.
- 在老年小鼠和通过NR4A2敲击和干扰素刺激评估效果.
主要成果:
- [a]二烯通过NR4A2上调ACE2和TMPRSS2的表达,增强SARS-CoV-2的进入.
- 这种影响独立于ACE2/TMPRSS2遗传变异.
- 在细胞和动物模型中观察到对SARS-CoV-2感染的敏感性增加.
- 随着年龄的增长,NR4A2,ACE2和TMPRSS2的表达增加,促进物甲基化减少.
结论:
- [a]烯通过增强NR4A2介导的ACE2和TMPRSS2表达来促进SARS-CoV-2感染.
- 调查结果澄清了吸烟对COVID-19严重性的影响,并建议对包括老年人在内的弱势群体进行潜在的预防策略.
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