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Article

Role of Human Antigen R (HuR) in the Regulation of Pulmonary ACE2 Expression

by
Noof Aloufi
1,2,3,4,
Zahraa Haidar
1,2,5,
Jun Ding
1,2,5,
Parameswaran Nair
6,
Andrea Benedetti
2,5,7,
David H. Eidelman
1,2,5,
Imed-Eddine Gallouzi
8,9,
Sergio Di Marco
8,
Sabah N. Hussain
1,2,3,5 and
Carolyn J. Baglole
1,2,3,5,10,*
1
Meakins-Christie Laboratories, Research Institute of the McGill University Health Centre (RI-MUHC), Montreal, QC H4A 3J1, Canada
2
Translational Research in Respiratory Diseases Program, Research Institute of the McGill University Health Centre, Montreal, QC H4A 3J1, Canada
3
Departments of Pathology, McGill University, Montreal, QC H3A 2B4, Canada
4
Department of Medical Laboratory Technology, Taibah University, Universities Road, Medina 42353, Saudi Arabia
5
Department of Medicine, McGill University, Montreal, QC H4A 3J1, Canada
6
Department of Medicine, McMaster University & St Joseph’s Healthcare, Hamilton, ON L8N 4A6, Canada
7
Department of Epidemiology, Biostatistics & Occupational Health, McGill University, Montreal, QC H3A 1G1, Canada
8
Department of Biochemistry, McGill University, Montreal, QC H3G 1Y6, Canada
9
Smart-Health Initiative and Biological and Environmental Science and Engineering (BESE) Division, King Abdullah University of Science and Technology (KAUST), Thuwal, Jeddah 23955, Saudi Arabia
10
Department of Pharmacology and Therapeutics, McGill University, Montreal, QC H3G 1Y6, Canada
*
Author to whom correspondence should be addressed.
Cells 2022, 11(1), 22; https://doi.org/10.3390/cells11010022
Submission received: 25 October 2021 / Revised: 13 December 2021 / Accepted: 19 December 2021 / Published: 22 December 2021
(This article belongs to the Special Issue Advances in COPD)
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Abstract

Patients with COPD may be at an increased risk for severe illness from COVID-19 because of ACE2 upregulation, the entry receptor for SARS-CoV-2. Chronic exposure to cigarette smoke, the main risk factor for COPD, increases pulmonary ACE2. How ACE2 expression is controlled is not known but may involve HuR, an RNA binding protein that increases protein expression by stabilizing mRNA. We hypothesized that HuR would increase ACE2 protein expression. We analyzed scRNA-seq data to profile ELAVL1 expression in distinct respiratory cell populations in COVID-19 and COPD patients. HuR expression and cellular localization was evaluated in COPD lung tissue by multiplex immunohistochemistry and in human lung cells by imaging flow cytometry. The regulation of ACE2 expression was evaluated using siRNA-mediated knockdown of HuR. There is a significant positive correlation between ELAVL1 and ACE2 in COPD cells. HuR cytoplasmic localization is higher in smoker and COPD lung tissue; there were also higher levels of cleaved HuR (CP-1). HuR binds to ACE2 mRNA but knockdown of HuR does not change ACE2 protein levels in primary human lung fibroblasts (HLFs). Our work is the first to investigate the association between ACE2 and HuR. Further investigation is needed to understand the mechanistic underpinning behind the regulation of ACE2 expression.
Keywords: HuR; ACE2; fibroblast; COVID-19; chronic obstructive pulmonary disease; ELAVL1 HuR; ACE2; fibroblast; COVID-19; chronic obstructive pulmonary disease; ELAVL1

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MDPI and ACS Style

Aloufi, N.; Haidar, Z.; Ding, J.; Nair, P.; Benedetti, A.; Eidelman, D.H.; Gallouzi, I.-E.; Di Marco, S.; Hussain, S.N.; Baglole, C.J. Role of Human Antigen R (HuR) in the Regulation of Pulmonary ACE2 Expression. Cells 2022, 11, 22. https://doi.org/10.3390/cells11010022

AMA Style

Aloufi N, Haidar Z, Ding J, Nair P, Benedetti A, Eidelman DH, Gallouzi I-E, Di Marco S, Hussain SN, Baglole CJ. Role of Human Antigen R (HuR) in the Regulation of Pulmonary ACE2 Expression. Cells. 2022; 11(1):22. https://doi.org/10.3390/cells11010022

Chicago/Turabian Style

Aloufi, Noof, Zahraa Haidar, Jun Ding, Parameswaran Nair, Andrea Benedetti, David H. Eidelman, Imed-Eddine Gallouzi, Sergio Di Marco, Sabah N. Hussain, and Carolyn J. Baglole. 2022. "Role of Human Antigen R (HuR) in the Regulation of Pulmonary ACE2 Expression" Cells 11, no. 1: 22. https://doi.org/10.3390/cells11010022

APA Style

Aloufi, N., Haidar, Z., Ding, J., Nair, P., Benedetti, A., Eidelman, D. H., Gallouzi, I.-E., Di Marco, S., Hussain, S. N., & Baglole, C. J. (2022). Role of Human Antigen R (HuR) in the Regulation of Pulmonary ACE2 Expression. Cells, 11(1), 22. https://doi.org/10.3390/cells11010022

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