Expression of the SARS-CoV-2 ACE2 Receptor in the Human Airway Epithelium
Expression of the SARS-CoV-2 ACE2 Receptor in the Human Airway Epithelium
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DOI：
10.1164/rccm.202003-0541oc
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发表时间：
2020-07-15
影响因子：
24.7
通讯作者：
Crystal, Ronald G.
中科院分区：
文献类型：
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作者：
Zhang, Haijun;Rostami, Mahboubeh R.;Crystal, Ronald G.
基本原理：感染严重急性呼吸综合征冠状病毒2（SARS-CoV-2）会导致冠状病毒病（COVID-19），这是一种主要的呼吸道疾病。SARS-CoV-2感染的第一步是病毒与ACE 2结合（血管紧张素转换酶2）对气道上皮的影响。目的：目的是了解ACE 2在人气道上皮中的表达。方法：通过气管纤维支气管镜采集气道上皮细胞，大气道上皮细胞（LAE），使用微阵列、RNA测序和10 ×单细胞转录组分析，分析非吸烟者和吸烟者的小气道上皮（SAE）中ACE 2和其他冠状病毒感染相关基因的表达，检测结果及主要结果：1）ACE 2在气管和LAE中的表达相似，SAE中表达较低; 2）SAE中ACE 2在基底细胞、中间细胞、棒状细胞、粘液细胞和纤毛细胞中均有表达; 3）SAE中ACE 2表达上调，男性明显上调; 4）miR-1246表达水平可能在吸烟者SAE中的ACE 2上调中起作用; 5）ACE 2在来自原代气道基底干细胞/祖细胞的气液界面培养物上体外分化的气道上皮中表达;这可以使用来自健康非吸烟者的LAE和SAE永生化基底细胞系复制。ACE 2是编码SARS-CoV-2受体的基因，在人气道上皮细胞中表达，其表达变化与SARS-CoV-2感染的初始步骤的生物学相关。
Rationale: Infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease (COVID-19), a predominantly respiratory illness. The first step in SARS-CoV-2 infection is binding of the virus to ACE2(angiotensin-converting enzyme 2) on the airway epithelium.Objectives: The objective was to gain insight into the expression of ACE2 in the human airway epithelium.Methods: Airway epithelia sampled by fiberoptic bronchoscopy of trachea, large airway epithelia (LAE), and small airway epithelia (SAE) of nonsmokers and smokers were analyzed for expression of ACE2 and other coronavirus infection-related genes using microarray, RNA sequencing, and 10x single-cell transcriptome analysis, with associated examination of ACE2-related microRNA.Measurements and Main Results: 1) ACE2 is expressed similarly in the trachea and LAE, with lower expression in the SAE; 2) in the SAE, ACE2 is expressed in basal, intermediate, club, mucus, and ciliated cells; 3) ACE2 is upregulated in the SAE by smoking, significantly in men; 4) levels of miR-1246 expression could play a role in ACE2 upregulation in the SAE of smokers; and 5) ACE2 is expressed in airway epithelium differentiated in vitro on air-liquid interface cultures from primary airway basal stem/progenitor cells; this can be replicated using LAE and SAE immortalized basal cell lines derived from healthy nonsmokers.Conclusions: ACE2, the gene encoding the receptor for SARS-CoV-2, is expressed in the human airway epithelium, with variations in expression relevant to the biology of initial steps in SARS-CoV-2 infection.