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肠道炎症调节 ACE2 和 TMPRSS2 的表达，并可能与 SARS-CoV-2 相关疾病的发病机制重叠。

Intestinal Inflammation Modulates the Expression of ACE2 and TMPRSS2 and Potentially Overlaps With the Pathogenesis of SARS-CoV-2-related Disease.

机构信息

Center for Biostatistics, Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, New York; Icahn Institute for Data Science and Genomic Technology, New York City, New York.

The Dr. Henry D. Janowitz Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York; Precision Institute of Immunology, Icahn School of Medicine at Mount Sinai, New York, New York.

出版信息

Gastroenterology. 2021 Jan;160(1):287-301.e20. doi: 10.1053/j.gastro.2020.09.029. Epub 2020 Sep 25.

DOI:
10.1053/j.gastro.2020.09.029
PMID:32980345
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7516468/
Abstract

BACKGROUND AND AIMS

The presence of gastrointestinal symptoms and high levels of viral RNA in the stool suggest active severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication within enterocytes.

METHODS

Here, in multiple, large cohorts of patients with inflammatory bowel disease (IBD), we have studied the intersections between Coronavirus Disease 2019 (COVID-19), intestinal inflammation, and IBD treatment.

RESULTS

A striking expression of ACE2 on the small bowel enterocyte brush border supports intestinal infectivity by SARS-CoV-2. Commonly used IBD medications, both biologic and nonbiologic, do not significantly impact ACE2 and TMPRSS2 receptor expression in the uninflamed intestines. In addition, we have defined molecular responses to COVID-19 infection that are also enriched in IBD, pointing to shared molecular networks between COVID-19 and IBD.

CONCLUSIONS

These data generate a novel appreciation of the confluence of COVID-19- and IBD-associated inflammation and provide mechanistic insights supporting further investigation of specific IBD drugs in the treatment of COVID-19. Preprint doi: https://doi.org/10.1101/2020.05.21.109124.

摘要

背景和目的

胃肠道症状和粪便中病毒 RNA 水平高提示肠上皮细胞内存在活跃的严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）复制。

方法

在这里，我们在多个大型炎症性肠病（IBD）患者队列中研究了 2019 年冠状病毒病（COVID-19）、肠道炎症和 IBD 治疗之间的交叉点。

结果

小肠肠上皮细胞刷状缘上 ACE2 的强烈表达支持 SARS-CoV-2 的肠道感染。常用的 IBD 药物，包括生物制剂和非生物制剂，在未发炎的肠道中对 ACE2 和 TMPRSS2 受体的表达没有显著影响。此外，我们还定义了对 COVID-19 感染的分子反应，这些反应在 IBD 中也更为丰富，表明 COVID-19 和 IBD 之间存在共同的分子网络。

结论

这些数据对 COVID-19 和 IBD 相关炎症的融合产生了新的认识，并提供了支持进一步研究特定 IBD 药物治疗 COVID-19 的机制见解。预印本 doi：https://doi.org/10.1101/2020.05.21.109124.

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