通过降低ACE2,FXR抑制可以防止SARS-CoV-2感染
Teresa Brevini1, Mailis Maes2, Gwilym J Webb3
1Wellcome-MRC Cambridge Stem Cell Institute, Cambridge, UK. tb647@cam.ac.uk.
Nature
|December 5, 2022
概括
法尔内索伊德X受体 (FXR) 直接控制血管酶转化酶2 (ACE2) 的表达,这是一个关键的SARS-CoV-2受体. 乌尔苏酸 (UDCA) 降低了ACE2,可能降低COVID-19的易感性.
科学领域:
- 分子生物学
- 病毒学
- 药理学
背景情况:
- ангиотензин转化酶2 (ACE2) 是SARS-CoV-2的一个关键宿主受体.
- 调节ACE2表达的机制尚未完全理解.
- 调节ACE2为COVID-19提供了一个潜在的化学预防策略.
研究的目的:
- 研究法内索伊德X受体 (FXR) 在调节ACE2转录中的作用.
- 评估FXR调节剂,特别是ursodeoxycholic acid (UDCA) 在降低ACE2和降低SARS-CoV-2易感性的有效性.
主要方法:
- 在相关的人类和动物模型中研究了FXR作为ACE2转录的直接调节者.
- 使用z-guggulsterone和UDCA调节器官和组织中的FXR信号和ACE2表达.
- 在体外,体外和体外评估SARS-CoV-2感染易感性.
- 分析了临床注册数据和肝移植队列,以将UDCA治疗与临床结果相关联.
主要成果:
- 在多种组织中,FXR被确定为ACE2转录的直接调节者.
- 在人体器官,动物模型和人体器官中,UDCA成功降低了ACE2的表达.
- 在感染SARS-CoV-2的患者中,UDCA治疗与改善的临床结果相关,包括肝移植患者.
结论:
- 在控制ACE2表达方面,FXR起着重要作用.
- 通过UDCA调节FXR-ACE2通路,可以减少SARS-CoV-2感染并改善临床结果.
- 需要进一步进行临床试验,以探索UDCA作为COVID-19的治疗干预措施.
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