Airways Expression of SARS-CoV-2 Receptor, ACE2, and TMPRSS2 Is Lower in Children Than Adults and Increases with Smoking and COPD

Airways Expression of SARS-CoV-2 Receptor, ACE2, and TMPRSS2 Is Lower in Children Than Adults and Increases with Smoking and COPD
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DOI:
10.1016/j.omtm.2020.05.013
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发表时间:
2020-09-11
期刊:
MOLECULAR THERAPY METHODS & CLINICAL DEVELOPMENT
影响因子:
--
通讯作者:
Halwani, Rabih
Halwani, Rabih
中科院分区:
其他
文献类型:
--
作者:
Sharif-Askari, Narjes Saheb;Sharif-Askari, Fatemeh Saheb;Halwani, Rabih

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据报道,血管紧张素转换酶2(ACE2)和跨膜丝氨酸蛋白酶2(TMPRSS2)是严重急性呼吸综合征冠状病毒2型(SARS-CoV-2)的主要进入蛋白,在引起冠状病毒病2019(新冠肺炎)中起关键作用。为了研究这些SARS-CoV-2宿主细胞进入基因在肺部的表达水平,我们使用了公共基因表达数据集。我们发现ACE2和TMPRSS2在鼻腔和支气管呼吸道中的表达与年龄和疾病状态有关。研究发现,儿童上呼吸道和下呼吸道(鼻和支气管)新冠肺炎受体的表达明显降低。此外,在吸烟者和慢性阻塞性肺疾病(COPD)患者中,ACE2和TMPRSS2的表达均显著高于非吸烟者和健康人。ACE2和TMPRSS2在儿童和成人、COPD和糖尿病患者之间的血液表达水平没有差异。然而,这些基因的血液表达水平在高血压患者中显著增加,而哮喘患者的血液中只有ACE2上调。这些结果表明,观察到的儿童和成人新冠肺炎严重程度的差异可能部分归因于ACE2和TMPRSS2呼吸道组织表达水平的差异。
It has been reported that angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) are the main cell entry proteins for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and play a critical role in causing coronavirus disease 2019 (COVID-19). To investigate the expression level of these SARS-CoV-2 host cell entry genes in the lung airway, we used public gene expression datasets. We have found a differential expression of ACE2 and TMPRSS2 in nasal and bronchial airways relative to age and diseases status. Children were found to have significantly lower expression of COVID-19 receptors in the upper and lower airways (nasal and bronchial). Moreover, the lung airway expression of both ACE2 and TMPRSS2 was found to be significantly upregulated in smokers compared with non-smokers, and in patients with chronic obstructive pulmonary disease (COPD) compared with healthy subjects. No difference was observed in the blood expression levels of ACE2 and TMPRSS2 between children and adults, or in COPD or diabetic patients. However, a significant increase in blood expression levels of these genes was observed in patients with essential hypertension, whereas only ACE2 was upregulated in the blood of asthmatics. These results suggest that the observed difference in COVID-19 severity between children and adults could, in part, be attributed to the difference in ACE2 and TMPRSS2 airways tissue expression levels.