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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

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...

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Autores principales: Lu, Wenying, Eapen, Mathew Suji, Singhera, Gurpreet Kaur, Markos, James, Haug, Greg, Chia, Collin, Larby, Josie, Brake, Samuel James, Westall, Glen P., Jaffar, Jade, Kalidhindi, Rama Satyanarayana Raju, Fonseka, Nimesha De, Sathish, Venkatachalem, Hackett, Tillie L., Sohal, Sukhwinder Singh
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8837032/
https://www.ncbi.nlm.nih.gov/pubmed/35160229
http://dx.doi.org/10.3390/jcm11030777
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author Lu, Wenying
Eapen, Mathew Suji
Singhera, Gurpreet Kaur
Markos, James
Haug, Greg
Chia, Collin
Larby, Josie
Brake, Samuel James
Westall, Glen P.
Jaffar, Jade
Kalidhindi, Rama Satyanarayana Raju
Fonseka, Nimesha De
Sathish, Venkatachalem
Hackett, Tillie L.
Sohal, Sukhwinder Singh
author_facet Lu, Wenying
Eapen, Mathew Suji
Singhera, Gurpreet Kaur
Markos, James
Haug, Greg
Chia, Collin
Larby, Josie
Brake, Samuel James
Westall, Glen P.
Jaffar, Jade
Kalidhindi, Rama Satyanarayana Raju
Fonseka, Nimesha De
Sathish, Venkatachalem
Hackett, Tillie L.
Sohal, Sukhwinder Singh
author_sort Lu, Wenying
collection PubMed
description 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.
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spelling pubmed-88370322022-02-12 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 Lu, Wenying Eapen, Mathew Suji Singhera, Gurpreet Kaur Markos, James Haug, Greg Chia, Collin Larby, Josie Brake, Samuel James Westall, Glen P. Jaffar, Jade Kalidhindi, Rama Satyanarayana Raju Fonseka, Nimesha De Sathish, Venkatachalem Hackett, Tillie L. Sohal, Sukhwinder Singh J Clin Med Article 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. MDPI 2022-01-31 /pmc/articles/PMC8837032/ /pubmed/35160229 http://dx.doi.org/10.3390/jcm11030777 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Lu, Wenying
Eapen, Mathew Suji
Singhera, Gurpreet Kaur
Markos, James
Haug, Greg
Chia, Collin
Larby, Josie
Brake, Samuel James
Westall, Glen P.
Jaffar, Jade
Kalidhindi, Rama Satyanarayana Raju
Fonseka, Nimesha De
Sathish, Venkatachalem
Hackett, Tillie L.
Sohal, Sukhwinder Singh
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
title 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_short 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
title_sort 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
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8837032/
https://www.ncbi.nlm.nih.gov/pubmed/35160229
http://dx.doi.org/10.3390/jcm11030777
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