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Respiratory Research
Published in: Respiratory Research 1/2020

Open Access 01-12-2020 | Coronavirus | Research

SARS-CoV-2 induces transcriptional signatures in human lung epithelial cells that promote lung fibrosis

Authors: Jincheng Xu, Xiaoyue Xu, Lina Jiang, Kamal Dua, Philip M. Hansbro, Gang Liu

Published in: Respiratory Research | Issue 1/2020

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Abstract

Background

Severe acute respiratory syndrome (SARS)-CoV-2-induced coronavirus disease-2019 (COVID-19) is a pandemic disease that affects > 2.8 million people worldwide, with numbers increasing dramatically daily. However, there is no specific treatment for COVID-19 and much remains unknown about this disease. Angiotensin-converting enzyme (ACE)2 is a cellular receptor of SARS-CoV-2. It is cleaved by type II transmembrane serine protease (TMPRSS)2 and disintegrin and metallopeptidase domain (ADAM)17 to assist viral entry into host cells. Clinically, SARS-CoV-2 infection may result in acute lung injury and lung fibrosis, but the underlying mechanisms of COVID-19 induced lung fibrosis are not fully understood.

Methods

The networks of ACE2 and its interacting molecules were identified using bioinformatic methods. Their gene and protein expressions were measured in human epithelial cells after 24 h SARS-CoV-2 infection, or in existing datasets of lung fibrosis patients.

Results

We confirmed the binding of SARS-CoV-2 and ACE2 by bioinformatic analysis. TMPRSS2, ADAM17, tissue inhibitor of metalloproteinase (TIMP)3, angiotensinogen (AGT), transformation growth factor beta (TGFB1), connective tissue growth factor (CTGF), vascular endothelial growth factor (VEGF) A and fibronectin (FN) were interacted with ACE2, and the mRNA and protein of these molecules were expressed in lung epithelial cells. SARS-CoV-2 infection increased ACE2, TGFB1, CTGF and FN1 mRNA that were drivers of lung fibrosis. These changes were also found in lung tissues from lung fibrosis patients.

Conclusions

Therefore, SARS-CoV-2 binds with ACE2 and activates fibrosis-related genes and processes to induce lung fibrosis.
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Metadata
Title
SARS-CoV-2 induces transcriptional signatures in human lung epithelial cells that promote lung fibrosis
Authors
Jincheng Xu
Xiaoyue Xu
Lina Jiang
Kamal Dua
Philip M. Hansbro
Gang Liu
Publication date
01-12-2020
Publisher
BioMed Central
Published in
Respiratory Research / Issue 1/2020
Electronic ISSN: 1465-993X
DOI
https://doi.org/10.1186/s12931-020-01445-6

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