University Of Tasmania
148750 - Angiotensin-converting enzyme 2 (ACE2) transmembrane.pdf (3.58 MB)

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

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posted on 2023-05-21, 05:38 authored by Wenying LuWenying Lu, Mathew Eapen, Singhera, GK, Markos, J, Haug, G, Chia, C, Josie LarbyJosie Larby, Samuel BrakeSamuel Brake, Westall, GP, Jaffar, J, Kalidhindi, RSR, De Fonseka, N, Sathish, V, Hackett, TL, Sukhwinder SohalSukhwinder Sohal
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.


LAM Australia Research Alliance


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Journal of Clinical Medicine



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School of Health Sciences



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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 (

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Diagnosis of human diseases and conditions

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