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Recombinant ACE2 protein protects against acute lung injury induced by SARS-CoV-2 spike RBD protein
BACKGROUND: SARS-CoV-2 infection leads to acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Both clinical data and animal experiments suggest that the renin–angiotensin system (RAS) is involved in the pathogenesis of SARS-CoV-2-induced ALI. Angiotensin-converting enzyme 2 (ACE2...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9178547/ https://www.ncbi.nlm.nih.gov/pubmed/35681221 http://dx.doi.org/10.1186/s13054-022-04034-9 |
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author | Zhang, Lingbing Zhang, Yandan Qin, Xia Jiang, Xuejun Zhang, Jun Mao, Lejiao Jiang, Ziqi Jiang, Yu Liu, Gang Qiu, Jingfu Chen, Chengzhi Qiu, Feng Zou, Zhen |
author_facet | Zhang, Lingbing Zhang, Yandan Qin, Xia Jiang, Xuejun Zhang, Jun Mao, Lejiao Jiang, Ziqi Jiang, Yu Liu, Gang Qiu, Jingfu Chen, Chengzhi Qiu, Feng Zou, Zhen |
author_sort | Zhang, Lingbing |
collection | PubMed |
description | BACKGROUND: SARS-CoV-2 infection leads to acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Both clinical data and animal experiments suggest that the renin–angiotensin system (RAS) is involved in the pathogenesis of SARS-CoV-2-induced ALI. Angiotensin-converting enzyme 2 (ACE2) is the functional receptor for SARS-CoV-2 and a crucial negative regulator of RAS. Recombinant ACE2 protein (rACE2) has been demonstrated to play protective role against SARS-CoV and avian influenza-induced ALI, and more relevant, rACE2 inhibits SARS-CoV-2 proliferation in vitro. However, whether rACE2 protects against SARS-CoV-2-induced ALI in animal models and the underlying mechanisms have yet to be elucidated. METHODS AND RESULTS: Here, we demonstrated that the SARS-CoV-2 spike receptor-binding domain (RBD) protein aggravated lipopolysaccharide (LPS)-induced ALI in mice. SARS-CoV-2 spike RBD protein directly binds and downregulated ACE2, leading to an elevation in angiotensin (Ang) II. AngII further increased the NOX1/2 through AT(1)R, subsequently causing oxidative stress and uncontrolled inflammation and eventually resulting in ALI/ARDS. Importantly, rACE2 remarkably reversed SARS-CoV-2 spike RBD protein-induced ALI by directly binding SARS-CoV-2 spike RBD protein, cleaving AngI or cleaving AngII. CONCLUSION: This study is the first to prove that rACE2 plays a protective role against SARS-CoV-2 spike RBD protein-aggravated LPS-induced ALI in an animal model and illustrate the mechanism by which the ACE2-AngII-AT(1)R-NOX1/2 axis might contribute to SARS-CoV-2-induced ALI. |
format | Online Article Text |
id | pubmed-9178547 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-91785472022-06-09 Recombinant ACE2 protein protects against acute lung injury induced by SARS-CoV-2 spike RBD protein Zhang, Lingbing Zhang, Yandan Qin, Xia Jiang, Xuejun Zhang, Jun Mao, Lejiao Jiang, Ziqi Jiang, Yu Liu, Gang Qiu, Jingfu Chen, Chengzhi Qiu, Feng Zou, Zhen Crit Care Research BACKGROUND: SARS-CoV-2 infection leads to acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Both clinical data and animal experiments suggest that the renin–angiotensin system (RAS) is involved in the pathogenesis of SARS-CoV-2-induced ALI. Angiotensin-converting enzyme 2 (ACE2) is the functional receptor for SARS-CoV-2 and a crucial negative regulator of RAS. Recombinant ACE2 protein (rACE2) has been demonstrated to play protective role against SARS-CoV and avian influenza-induced ALI, and more relevant, rACE2 inhibits SARS-CoV-2 proliferation in vitro. However, whether rACE2 protects against SARS-CoV-2-induced ALI in animal models and the underlying mechanisms have yet to be elucidated. METHODS AND RESULTS: Here, we demonstrated that the SARS-CoV-2 spike receptor-binding domain (RBD) protein aggravated lipopolysaccharide (LPS)-induced ALI in mice. SARS-CoV-2 spike RBD protein directly binds and downregulated ACE2, leading to an elevation in angiotensin (Ang) II. AngII further increased the NOX1/2 through AT(1)R, subsequently causing oxidative stress and uncontrolled inflammation and eventually resulting in ALI/ARDS. Importantly, rACE2 remarkably reversed SARS-CoV-2 spike RBD protein-induced ALI by directly binding SARS-CoV-2 spike RBD protein, cleaving AngI or cleaving AngII. CONCLUSION: This study is the first to prove that rACE2 plays a protective role against SARS-CoV-2 spike RBD protein-aggravated LPS-induced ALI in an animal model and illustrate the mechanism by which the ACE2-AngII-AT(1)R-NOX1/2 axis might contribute to SARS-CoV-2-induced ALI. BioMed Central 2022-06-09 /pmc/articles/PMC9178547/ /pubmed/35681221 http://dx.doi.org/10.1186/s13054-022-04034-9 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open 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 give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Zhang, Lingbing Zhang, Yandan Qin, Xia Jiang, Xuejun Zhang, Jun Mao, Lejiao Jiang, Ziqi Jiang, Yu Liu, Gang Qiu, Jingfu Chen, Chengzhi Qiu, Feng Zou, Zhen Recombinant ACE2 protein protects against acute lung injury induced by SARS-CoV-2 spike RBD protein |
title | Recombinant ACE2 protein protects against acute lung injury induced by SARS-CoV-2 spike RBD protein |
title_full | Recombinant ACE2 protein protects against acute lung injury induced by SARS-CoV-2 spike RBD protein |
title_fullStr | Recombinant ACE2 protein protects against acute lung injury induced by SARS-CoV-2 spike RBD protein |
title_full_unstemmed | Recombinant ACE2 protein protects against acute lung injury induced by SARS-CoV-2 spike RBD protein |
title_short | Recombinant ACE2 protein protects against acute lung injury induced by SARS-CoV-2 spike RBD protein |
title_sort | recombinant ace2 protein protects against acute lung injury induced by sars-cov-2 spike rbd protein |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9178547/ https://www.ncbi.nlm.nih.gov/pubmed/35681221 http://dx.doi.org/10.1186/s13054-022-04034-9 |
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