SARS-CoV-2 induces transcriptional signatures in human lung epithelial cells that promote lung fibrosis.
Respir Res
; 21(1): 182, 2020 Jul 14.
Article
in English
| MEDLINE | ID: covidwho-647112
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.Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Pneumonia, Viral
/
Pulmonary Fibrosis
/
Respiratory Distress Syndrome
/
Gene Expression Regulation
/
Coronavirus Infections
/
Peptidyl-Dipeptidase A
/
Severe acute respiratory syndrome-related coronavirus
Type of study:
Diagnostic study
/
Observational study
/
Prognostic study
Limits:
Female
/
Humans
/
Male
Country/Region as subject:
Asia
Language:
English
Journal:
Respir Res
Year:
2020
Document Type:
Article
Affiliation country:
S12931-020-01445-6
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