提米丁酸化酶驱动SARS-CoV-2尖端蛋白诱导的肺瘤发生
bioRxiv : the preprint server for biology
|December 31, 2025
概括
由于SARS-CoV-2的Spike protein (SP) 和thymidine phosphorylase (TYMP),COVID-19幸存者面临更高的肺癌风险. 缺少TYMP可减轻SP诱导的肺损伤和瘤发展,提供治疗点.
科学领域:
- 肺部医学 肺部医学
- 在瘤学瘤学.
- 病毒学 病毒学
背景情况:
- COVID-19幸存者显示间歇性肺纤维化增加,这是肺癌风险因素.
- 在促进肺部瘤发生方面,SARS-CoV-2尖端蛋白 (SP) 和胆氨酸酸酶 (TYMP) 的作用需要研究.
研究的目的:
- 为了调查SARS-CoV-2SP诱导的肺损伤和TYMP升高是否促进肺瘤发生.
- 探索TYMP作为一个潜在的治疗目标,以减轻COVID-19的长期肺部后果.
主要方法:
- 使用TrinetX的回顾性队列分析和K18-hACE2转基因小鼠 (有或没有TYMP缺乏症) 的机制研究.
- 小鼠接受了内SP或对照溶解物,随后进行了尿诱导的肺癌方案.
- 评估了肺损伤,炎症,纤维化,STAT3激活,细胞因子概况和瘤负担;在体外评估了SP和RBD诱导的ACE2处理.
主要成果:
- COVID-19幸存者表现出增加的肺癌风险 (HR 1.50),特别是目前的吸烟者.
- 在小鼠中,SP诱导肺损伤,炎症和微血栓,这些在TYMP缺乏的小鼠中减少.
- SP显著增加了肺瘤的发病率和攻击性;TYMP缺乏减少了瘤的形成从50%降至18%,并减弱了SP诱导的STAT3上调和纤维化.
结论:
- SARS-CoV-2 SP 驱动肺损伤,纤维化和瘤发生,通过一个依赖于 TYMP 的机制,涉及 STAT3 信号和炎症重塑.
- COVID-19显著增加了肺癌风险,特别是在目前的吸烟者中.
- TYMP是缓解COVID-19肺部长期后果的潜在治疗标.
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