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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

Citation

Lu, W and Eapen, MS and Singhera, GK and Markos, J and Haug, G and Chia, C and Larby, J and Brake, SJ and Westall, GP and Jaffar, J and Kalidhindi, RSR and De Fonseka, N and Sathish, V and Hackett, TL and 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, 11, (3) Article 777. ISSN 2077-0383 (2022) [Refereed Article]


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Copyright Statement

Copyright: 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons 4.0 International (CC BY 4.0) license (https://creativecommons.org/licenses/by/4.0/).

DOI: doi:10.3390/jcm11030777

Abstract

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.

Item Details

Item Type:Refereed Article
Keywords:COVID-19, IPF, ACE2, respiratory, SARS-CoV-2, fibrosis, LAM, epithelium, smoking
Research Division:Biomedical and Clinical Sciences
Research Group:Cardiovascular medicine and haematology
Research Field:Cardiology (incl. cardiovascular diseases)
Objective Division:Health
Objective Group:Clinical health
Objective Field:Diagnosis of human diseases and conditions
UTAS Author:Lu, W (Dr Monica Lu)
UTAS Author:Eapen, MS (Dr Mathew Eapen)
UTAS Author:Markos, J (Dr Jim Markos)
UTAS Author:Haug, G (Dr Greg Haug)
UTAS Author:Larby, J (Dr Josie Larby)
UTAS Author:Brake, SJ (Mr Sam Brake)
UTAS Author:Sohal, SS (Dr Sukhwinder Sohal)
ID Code:148750
Year Published:2022
Deposited By:Health Sciences
Deposited On:2022-02-06
Last Modified:2022-03-04
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