Int J Med Sci 2020; 17(11):1522-1531. doi:10.7150/ijms.46695

Research Paper

A comprehensive investigation of the mRNA and protein level of ACE2, the putative receptor of SARS-CoV-2, in human tissues and blood cells

Yiliang Wang1,3,4*, Yun Wang2*, Weisheng Luo1,3,4, Lianzhou Huang1,3,4, Ji Xiao1,3,4, Feng Li1,3,4, Shurong Qin1,3,4, Xiaowei Song1,3,4, Yanting Wu1,3,4, Qiongzhen Zeng1,3,4, Fujun Jin1,3,4, Yifei Wang1,3,4✉

1. Guangzhou Jinan Biomedicine Research and Development Center, Institute of Biomedicine, College of Life Science and Technology, Jinan University, Guangzhou 510632, PR China;
2. Department of Obstetrics and Gynecology, The First Affiliated Hospital of Jinan University, Guangzhou 510632, PR China;
3. Key Laboratory of Virology of Guangzhou, Jinan University, Guangzhou 510632, P.R, China;
4. Key Laboratory of Bioengineering Medicine of Guangdong Province, Jinan University, Guangzhou 510632, P.R, China.
*These authors contributed equally to this work.

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Citation:
Wang Y, Wang Y, Luo W, Huang L, Xiao J, Li F, Qin S, Song X, Wu Y, Zeng Q, Jin F, Wang Y. A comprehensive investigation of the mRNA and protein level of ACE2, the putative receptor of SARS-CoV-2, in human tissues and blood cells. Int J Med Sci 2020; 17(11):1522-1531. doi:10.7150/ijms.46695. Available from https://www.medsci.org/v17p1522.htm

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Abstract

The outbreak of pneumonia caused by SARS-CoV-2 posed a great threat to global human health, which urgently requires us to understand comprehensively the mechanism of SARS-CoV-2 infection. Angiotensin-converting enzyme 2 (ACE2) was identified as a functional receptor for SARS-CoV-2, distribution of which may indicate the risk of different human organs vulnerable to SARS-CoV-2 infection. Previous studies investigating the distribution of ACE2 mRNA in human tissues only involved a limited size of the samples and a lack of determination for ACE2 protein. Given the heterogeneity among humans, the datasets covering more tissues with a larger size of samples should be analyzed. Indeed, ACE2 is a membrane and secreted protein, while the expression of ACE2 in blood and common blood cells remains unknown. Herein, the proteomic data in HIPED and the antibody-based immunochemistry result in HPA were collected to analyze the distribution of ACE2 protein in human tissues. The bulk RNA-seq profiles from three separate public datasets including HPA tissue Atlas, GTEx, and FANTOM5 CAGE were also obtained to determine the expression of ACE2 in human tissues. Moreover, the abundance of ACE2 in human blood and blood cells was determined by analyzing the data in the PeptideAtlas and the HPA Blood Atlas. We found that the mRNA expression cannot reflect the abundance of ACE2 factor due to the strong differences between mRNA and protein quantities of ACE2 within and across tissues. Our results suggested that ACE2 protein is mainly expressed in the small intestine, kidney, gallbladder, and testis, while the abundance of which in brain-associated tissues and blood common cells is low. HIPED revealed enrichment of ACE2 protein in the placenta and ovary despite a low mRNA level. Further, human secretome shows that the average concentration of ACE2 protein in the plasma of males is higher than those in females. Our research will be beneficial for understanding the transmission routes and sex-based differences in susceptibility of SARS-CoV-2 infection.

Keywords: SARS-CoV-2, Angiotensin-converting enzyme 2, Human tissues, Blood cells