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.

Autor: Lu W; Respiratory Translational Research Group, Department of Laboratory Medicine, School of Health Sciences, College of Health and Medicine, University of Tasmania, Launceston, TAS 7248, Australia.; 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., Eapen MS; Respiratory Translational Research Group, Department of Laboratory Medicine, School of Health Sciences, College of Health and Medicine, University of Tasmania, Launceston, TAS 7248, Australia.; 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., Singhera GK; Department of Anesthesiology, Pharmacology & Therapeutics, University of British Columbia, Vancouver, BC V6Z 1Y6, Canada.; UBC Centre for Heart Lung Innovation, St. Paul's Hospital, Vancouver, BC V6Z 1Y6, Canada., Markos J; Respiratory Translational Research Group, Department of Laboratory Medicine, School of Health Sciences, College of Health and Medicine, University of Tasmania, Launceston, TAS 7248, Australia.; Department of Respiratory Medicine, Launceston General Hospital, Launceston, TAS 7250, Australia., Haug G; Respiratory Translational Research Group, Department of Laboratory Medicine, School of Health Sciences, College of Health and Medicine, University of Tasmania, Launceston, TAS 7248, Australia.; Department of Respiratory Medicine, Launceston General Hospital, Launceston, TAS 7250, Australia., Chia C; Respiratory Translational Research Group, Department of Laboratory Medicine, School of Health Sciences, College of Health and Medicine, University of Tasmania, Launceston, TAS 7248, Australia.; Department of Respiratory Medicine, Launceston General Hospital, Launceston, TAS 7250, Australia., Larby J; Respiratory Translational Research Group, Department of Laboratory Medicine, School of Health Sciences, College of Health and Medicine, University of Tasmania, Launceston, TAS 7248, Australia.; Department of Respiratory Medicine, Launceston General Hospital, Launceston, TAS 7250, Australia., Brake SJ; Respiratory Translational Research Group, Department of Laboratory Medicine, School of Health Sciences, College of Health and Medicine, University of Tasmania, Launceston, TAS 7248, Australia., Westall GP; Department of Allergy, Immunology and Respiratory Medicine, The Alfred Hospital, Melbourne, VIC 3004, Australia.; Department of Immunology and Pathology, Monash University, Melbourne, VIC 3800, Australia., Jaffar J; Department of Allergy, Immunology and Respiratory Medicine, The Alfred Hospital, Melbourne, VIC 3004, Australia.; Department of Immunology and Pathology, Monash University, Melbourne, VIC 3800, Australia., Kalidhindi RSR; Department of Pharmaceutical Sciences, School of Pharmacy, College of Health Professions, North Dakota State University, Fargo, ND 58105, USA., Fonseka N; Department of Pharmaceutical Sciences, School of Pharmacy, College of Health Professions, North Dakota State University, Fargo, ND 58105, USA., Sathish V; Department of Pharmaceutical Sciences, School of Pharmacy, College of Health Professions, North Dakota State University, Fargo, ND 58105, USA., Hackett TL; Department of Anesthesiology, Pharmacology & Therapeutics, University of British Columbia, Vancouver, BC V6Z 1Y6, Canada.; UBC Centre for Heart Lung Innovation, St. Paul's Hospital, Vancouver, BC V6Z 1Y6, Canada., Sohal SS; Respiratory Translational Research Group, Department of Laboratory Medicine, School of Health Sciences, College of Health and Medicine, University of Tasmania, Launceston, TAS 7248, Australia.
Jazyk: angličtina
Zdroj: Journal of clinical medicine [J Clin Med] 2022 Jan 31; Vol. 11 (3). Date of Electronic Publication: 2022 Jan 31.
DOI: 10.3390/jcm11030777
Abstrakt: 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.
Databáze: MEDLINE
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