Expression of the SARS-CoV-2 cell receptor gene ACE2 in a wide variety of human tissues

Expression of the SARS-CoV-2 cell receptor gene ACE2 in a wide variety of human tissues
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DOI:
10.1186/s40249-020-00662-x
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发表时间:
2020-04-28
影响因子:
8.1
通讯作者:
Wang, Xiao-Sheng
Wang, Xiao-Sheng
中科院分区:
医学1区
文献类型:
--
作者:
Li, Meng-Yuan;Li, Lin;Wang, Xiao-Sheng

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自2019年12月发现以来,严重急性呼吸综合征冠状病毒2(SARS-CoV-2)已在全球感染了超过218万人,截至2020年4月16日,已造成超过15万人死亡。SARS-CoV-2是引起2019冠状病毒病(COVID-19)的病毒,使用血管紧张素转换酶2(ACE2)作为细胞受体侵入人体细胞。因此,ACE2是理解SARS-CoV-2感染机制的关键。本研究旨在研究ACE2在不同组织中的表达情况,为进一步研究SARS-CoV-2感染机制提供理论依据。方法采用双侧Student t检验比较31例正常人组织中ACE2的表达水平,包括男性、女性和年轻人(年龄49岁)。我们还使用Pearson相关性检验研究了各种组织中ACE2表达和免疫特征之间的相关性。结果ACE2在小肠、睾丸、肾脏、心脏、甲状腺和脂肪组织中表达量最高,在血液、脾脏、骨髓、脑、血管和肌肉中表达量最低。ACE2在肺、结肠、肝脏、膀胱和肾上腺中显示中等表达水平。ACE2在男性和女性之间或年轻人和老年人之间的任何组织中均无差异表达。在皮肤、消化系统、脑和血管中,ACE2表达水平与男性和女性的免疫特征呈正相关。在甲状腺和肺中,ACE2表达水平分别与男性和女性的免疫特征呈正相关和负相关,在肺中,它们分别与老年组和年轻组呈正相关和负相关。结论SARS-CoV-2可感染除肺外的其他组织,且不同性别、年龄和种族的人感染率相同。不同的宿主对SARS-CoV-2感染的免疫反应可能部分解释了为什么男性和女性,年轻人和老年人感染这种病毒后疾病的严重程度明显不同。这项研究为ACE2在SARS-CoV-2大流行中的作用提供了新的见解。
Background Since its discovery in December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected more than 2 180 000 people worldwide and has caused more than 150 000 deaths as of April 16, 2020. SARS-CoV-2, which is the virus causing coronavirus disease 2019 (COVID-19), uses the angiotensin-converting enzyme 2 (ACE2) as a cell receptor to invade human cells. Thus, ACE2 is the key to understanding the mechanism of SARS-CoV-2 infection. This study is to investigate the ACE2 expression in various human tissues in order to provide insights into the mechanism of SARS-CoV-2 infection. Methods We compared ACE2 expression levels across 31 normal human tissues between males and females and between younger (ages 49 years) persons using two-sided Student's t test. We also investigated the correlations between ACE2 expression and immune signatures in various tissues using Pearson's correlation test. Results ACE2 expression levels were the highest in the small intestine, testis, kidneys, heart, thyroid, and adipose tissue, and were the lowest in the blood, spleen, bone marrow, brain, blood vessels, and muscle. ACE2 showed medium expression levels in the lungs, colon, liver, bladder, and adrenal gland. ACE2 was not differentially expressed between males and females or between younger and older persons in any tissue. In the skin, digestive system, brain, and blood vessels, ACE2 expression levels were positively associated with immune signatures in both males and females. In the thyroid and lungs, ACE2 expression levels were positively and negatively associated with immune signatures in males and females, respectively, and in the lungs they had a positive and a negative correlation in the older and younger groups, respectively. Conclusions Our data indicate that SARS-CoV-2 may infect other tissues aside from the lungs and infect persons with different sexes, ages, and races equally. The different host immune responses to SARS-CoV-2 infection may partially explain why males and females, young and old persons infected with this virus have markedly distinct disease severity. This study provides new insights into the role of ACE2 in the SARS-CoV-2 pandemic.