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Article

Angiotensin-Converting Enzyme 2 (ACE2), Transmembrane Peptidase Serine 2 (TMPRSS2), and Furin Expression Increases in the Lungs of Patients with Idiopathic Pulmonary Fibrosis (IPF) and Lymphangioleiomyomatosis (LAM): Implications for SARS-CoV-2 (COVID-19) Infections

1
Respiratory Translational Research Group, Department of Laboratory Medicine, School of Health Sciences, College of Health and Medicine, University of Tasmania, Launceston, TAS 7248, Australia
2
National Health and Medical Research Council (NHMRC) Centre of Research Excellence (CRE) in Pulmonary Fibrosis, Respiratory Medicine and Sleep Unit, Royal Prince Alfred Hospital, Camperdown, NSW 2050, Australia
3
Department of Anesthesiology, Pharmacology & Therapeutics, University of British Columbia, Vancouver, BC V6Z 1Y6, Canada
4
UBC Centre for Heart Lung Innovation, St. Paul’s Hospital, Vancouver, BC V6Z 1Y6, Canada
5
Department of Respiratory Medicine, Launceston General Hospital, Launceston, TAS 7250, Australia
6
Department of Allergy, Immunology and Respiratory Medicine, The Alfred Hospital, Melbourne, VIC 3004, Australia
7
Department of Immunology and Pathology, Monash University, Melbourne, VIC 3800, Australia
8
Department of Pharmaceutical Sciences, School of Pharmacy, College of Health Professions, North Dakota State University, Fargo, ND 58105, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Wolfram Windisch
J. Clin. Med. 2022, 11(3), 777; https://doi.org/10.3390/jcm11030777
Received: 20 January 2022 / Accepted: 24 January 2022 / Published: 31 January 2022
We previously reported higher ACE2 levels in smokers and patients with COPD. The current study investigates if patients with interstitial lung diseases (ILDs) such as IPF and LAM have elevated ACE2, TMPRSS2, and Furin levels, increasing their risk for SARS-CoV-2 infection and development of COVID-19. Surgically resected lung tissue from IPF, LAM patients, and healthy controls (HC) was immunostained for ACE2, TMPRSS2, and Furin. Percentage ACE2, TMPRSS2, and Furin expression was measured in small airway epithelium (SAE) and alveolar areas using computer-assisted Image-Pro Plus 7.0 software. IPF and LAM tissue was also immunostained for myofibroblast marker α-smooth muscle actin (α-SMA) and growth factor transforming growth factor beta1 (TGF-β1). Compared to HC, ACE2, TMPRSS2 and Furin expression were significantly upregulated in the SAE of IPF (p < 0.01) and LAM (p < 0.001) patients, and in the alveolar areas of IPF (p < 0.001) and LAM (p < 0.01). There was a significant positive correlation between smoking history and ACE2 expression in the IPF cohort for SAE (r = 0.812, p < 0.05) and alveolar areas (r = 0.941, p < 0.01). This, to our knowledge, is the first study to compare ACE2, TMPRSS2, and Furin expression in patients with IPF and LAM compared to HC. Descriptive images show that α-SMA and TGF-β1 increase in the IPF and LAM tissue. Our data suggests that patients with ILDs are at a higher risk of developing severe COVID-19 infection and post-COVID-19 interstitial pulmonary fibrosis. Growth factors secreted by the myofibroblasts, and surrounding tissue could further affect COVID-19 adhesion proteins/cofactors and post-COVID-19 interstitial pulmonary fibrosis. Smoking seems to be the major driving factor in patients with IPF. View Full-Text
Keywords: ACE2; TMPRSS2; Furin; IPF; LAM; COVID-19 ACE2; TMPRSS2; Furin; IPF; LAM; COVID-19
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MDPI and ACS Style

Lu, W.; Eapen, M.S.; Singhera, G.K.; Markos, J.; Haug, G.; Chia, C.; Larby, J.; Brake, S.J.; Westall, G.P.; Jaffar, J.; Kalidhindi, R.S.R.; Fonseka, N.D.; Sathish, V.; Hackett, T.L.; Sohal, S.S. Angiotensin-Converting Enzyme 2 (ACE2), Transmembrane Peptidase Serine 2 (TMPRSS2), and Furin Expression Increases in the Lungs of Patients with Idiopathic Pulmonary Fibrosis (IPF) and Lymphangioleiomyomatosis (LAM): Implications for SARS-CoV-2 (COVID-19) Infections. J. Clin. Med. 2022, 11, 777. https://doi.org/10.3390/jcm11030777

AMA Style

Lu W, Eapen MS, Singhera GK, Markos J, Haug G, Chia C, Larby J, Brake SJ, Westall GP, Jaffar J, Kalidhindi RSR, Fonseka ND, Sathish V, Hackett TL, Sohal SS. Angiotensin-Converting Enzyme 2 (ACE2), Transmembrane Peptidase Serine 2 (TMPRSS2), and Furin Expression Increases in the Lungs of Patients with Idiopathic Pulmonary Fibrosis (IPF) and Lymphangioleiomyomatosis (LAM): Implications for SARS-CoV-2 (COVID-19) Infections. Journal of Clinical Medicine. 2022; 11(3):777. https://doi.org/10.3390/jcm11030777

Chicago/Turabian Style

Lu, Wenying, Mathew Suji Eapen, Gurpreet Kaur Singhera, James Markos, Greg Haug, Collin Chia, Josie Larby, Samuel James Brake, Glen P. Westall, Jade Jaffar, Rama Satyanarayana Raju Kalidhindi, Nimesha De Fonseka, Venkatachalem Sathish, Tillie L. Hackett, and Sukhwinder Singh Sohal. 2022. "Angiotensin-Converting Enzyme 2 (ACE2), Transmembrane Peptidase Serine 2 (TMPRSS2), and Furin Expression Increases in the Lungs of Patients with Idiopathic Pulmonary Fibrosis (IPF) and Lymphangioleiomyomatosis (LAM): Implications for SARS-CoV-2 (COVID-19) Infections" Journal of Clinical Medicine 11, no. 3: 777. https://doi.org/10.3390/jcm11030777

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