SARS-CoV-2 induces transcriptional signatures in human lung epithelial cells that promote lung fibrosis.
- Publisher:
- BMC
- Publication Type:
- Journal Article
- Citation:
- Respiratory research, 2020, 21, (1)
- Issue Date:
- 2020-07-14
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Full metadata record
Field | Value | Language |
---|---|---|
dc.contributor.author | Xu, J | |
dc.contributor.author |
Xu, X https://orcid.org/0000-0003-4787-6547 |
|
dc.contributor.author | Jiang, L | |
dc.contributor.author |
Dua, K https://orcid.org/0000-0002-7507-1159 |
|
dc.contributor.author | Hansbro, PM | |
dc.contributor.author |
Liu, G https://orcid.org/0000-0002-0489-2638 |
|
dc.date.accessioned | 2020-09-16T07:06:03Z | |
dc.date.available | 2020-07-06 | |
dc.date.available | 2020-09-16T07:06:03Z | |
dc.date.issued | 2020-07-14 | |
dc.identifier.citation | Respiratory research, 2020, 21, (1) | |
dc.identifier.issn | 1465-9921 | |
dc.identifier.issn | 1465-993X | |
dc.identifier.uri | http://hdl.handle.net/10453/142707 | |
dc.description.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. | |
dc.format | Electronic | |
dc.language | eng | |
dc.publisher | BMC | |
dc.relation | http://purl.org/au-research/grants/nhmrc/1175134 | |
dc.relation.ispartof | Respiratory research | |
dc.relation.isbasedon | 10.1186/s12931-020-01445-6 | |
dc.rights | info:eu-repo/semantics/restrictedAccess | |
dc.rights | © The Author(s). 2020Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License,which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you giveappropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate ifchanges were made. The images or other third party material in this article are included in the article's Creative Commonslicence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commonslicence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtainpermission directly from the copyright holder. To view a copy of this licence, visithttp://creativecommons.org/licenses/by/4.0/.The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to thedata made available in this article, unless otherwise stated in a credit line to the data | |
dc.subject | 1102 Cardiorespiratory Medicine and Haematology, 1103 Clinical Sciences | |
dc.subject.classification | Respiratory System | |
dc.subject.mesh | Epithelial Cells | |
dc.subject.mesh | Humans | |
dc.subject.mesh | SARS Virus | |
dc.subject.mesh | Pneumonia, Viral | |
dc.subject.mesh | Coronavirus Infections | |
dc.subject.mesh | Pulmonary Fibrosis | |
dc.subject.mesh | Respiratory Distress Syndrome, Adult | |
dc.subject.mesh | Disease Progression | |
dc.subject.mesh | Peptidyl-Dipeptidase A | |
dc.subject.mesh | Receptors, Virus | |
dc.subject.mesh | Prevalence | |
dc.subject.mesh | Risk Assessment | |
dc.subject.mesh | Survival Analysis | |
dc.subject.mesh | Transcription, Genetic | |
dc.subject.mesh | Gene Expression Regulation | |
dc.subject.mesh | China | |
dc.subject.mesh | Female | |
dc.subject.mesh | Male | |
dc.subject.mesh | Transcriptional Activation | |
dc.subject.mesh | Pandemics | |
dc.subject.mesh | Epithelial Cells | |
dc.subject.mesh | Humans | |
dc.subject.mesh | SARS Virus | |
dc.subject.mesh | Pneumonia, Viral | |
dc.subject.mesh | Coronavirus Infections | |
dc.subject.mesh | Pulmonary Fibrosis | |
dc.subject.mesh | Respiratory Distress Syndrome, Adult | |
dc.subject.mesh | Disease Progression | |
dc.subject.mesh | Peptidyl-Dipeptidase A | |
dc.subject.mesh | Receptors, Virus | |
dc.subject.mesh | Prevalence | |
dc.subject.mesh | Risk Assessment | |
dc.subject.mesh | Survival Analysis | |
dc.subject.mesh | Transcription, Genetic | |
dc.subject.mesh | Gene Expression Regulation | |
dc.subject.mesh | China | |
dc.subject.mesh | Female | |
dc.subject.mesh | Male | |
dc.subject.mesh | Transcriptional Activation | |
dc.subject.mesh | Pandemics | |
dc.subject.mesh | China | |
dc.subject.mesh | Coronavirus Infections | |
dc.subject.mesh | Disease Progression | |
dc.subject.mesh | Epithelial Cells | |
dc.subject.mesh | Female | |
dc.subject.mesh | Gene Expression Regulation | |
dc.subject.mesh | Humans | |
dc.subject.mesh | Male | |
dc.subject.mesh | Pandemics | |
dc.subject.mesh | Peptidyl-Dipeptidase A | |
dc.subject.mesh | Pneumonia, Viral | |
dc.subject.mesh | Prevalence | |
dc.subject.mesh | Pulmonary Fibrosis | |
dc.subject.mesh | Receptors, Virus | |
dc.subject.mesh | Respiratory Distress Syndrome, Adult | |
dc.subject.mesh | Risk Assessment | |
dc.subject.mesh | SARS Virus | |
dc.subject.mesh | Survival Analysis | |
dc.subject.mesh | Transcription, Genetic | |
dc.subject.mesh | Transcriptional Activation | |
dc.title | SARS-CoV-2 induces transcriptional signatures in human lung epithelial cells that promote lung fibrosis. | |
dc.type | Journal Article | |
utslib.citation.volume | 21 | |
utslib.location.activity | England | |
utslib.for | 0601 Biochemistry and Cell Biology | |
utslib.for | 1102 Cardiorespiratory Medicine and Haematology | |
utslib.for | 1103 Clinical Sciences | |
utslib.for | 1102 Cardiorespiratory Medicine and Haematology | |
utslib.for | 1103 Clinical Sciences | |
pubs.organisational-group | /University of Technology Sydney/Faculty of Health | |
pubs.organisational-group | /University of Technology Sydney/Faculty of Health/Graduate School of Health/GSH.Pharmacy | |
pubs.organisational-group | /University of Technology Sydney | |
pubs.organisational-group | /University of Technology Sydney/Faculty of Health/Graduate School of Health | |
pubs.organisational-group | /University of Technology Sydney/Faculty of Science | |
pubs.organisational-group | /University of Technology Sydney/Faculty of Science/School of Life Sciences | |
utslib.copyright.status | recently_added | * |
pubs.consider-herdc | false | |
dc.date.updated | 2020-09-16T07:05:30Z | |
pubs.issue | 1 | |
pubs.publication-status | Published | |
pubs.volume | 21 | |
utslib.citation.issue | 1 |
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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