Matrix Metalloproteinases Expression Is Associated with SARS-CoV-2-Induced Lung Pathology and Extracellular-Matrix Remodeling in K18-hACE2 Mice

The COVID-19 pandemic caused by the SARS-CoV-2 infection induced lung inflammation characterized by cytokine storm and fulminant immune response of both resident and migrated immune cells, accelerating alveolar damage. In this work we identified members of the matrix metalloprotease (MMPs) family as...

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Main Authors: Hila Gutman, Moshe Aftalion, Sharon Melamed, Boaz Politi, Reinat Nevo, Sapir Havusha-Laufer, Hagit Achdout, David Gur, Tomer Israely, Shlomit Dachir, Emanuelle Mamroud, Irit Sagi, Yaron Vagima
Format: Article
Language:English
Published: MDPI AG 2022-07-01
Series:Viruses
Subjects:
Online Access:https://www.mdpi.com/1999-4915/14/8/1627
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author Hila Gutman
Moshe Aftalion
Sharon Melamed
Boaz Politi
Reinat Nevo
Sapir Havusha-Laufer
Hagit Achdout
David Gur
Tomer Israely
Shlomit Dachir
Emanuelle Mamroud
Irit Sagi
Yaron Vagima
author_facet Hila Gutman
Moshe Aftalion
Sharon Melamed
Boaz Politi
Reinat Nevo
Sapir Havusha-Laufer
Hagit Achdout
David Gur
Tomer Israely
Shlomit Dachir
Emanuelle Mamroud
Irit Sagi
Yaron Vagima
author_sort Hila Gutman
collection DOAJ
description The COVID-19 pandemic caused by the SARS-CoV-2 infection induced lung inflammation characterized by cytokine storm and fulminant immune response of both resident and migrated immune cells, accelerating alveolar damage. In this work we identified members of the matrix metalloprotease (MMPs) family associated with lung extra-cellular matrix (ECM) destruction using K18-hACE2-transgenic mice (K18-hACE2) infected intranasally with SARS-CoV-2. Five days post infection, the lungs exhibited overall alveolar damage of epithelial cells and massive leukocytes infiltration. A substantial pulmonary increase in MMP8, MMP9, and MMP14 in the lungs post SARS-CoV-2 infection was associated with degradation of ECM components including collagen, laminin, and proteoglycans. The process of tissue damage and ECM degradation during SARS-CoV-2 lung infection is suggested to be associated with activity of members of the MMPs family, which in turn may be used as a therapeutic intervention.
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spelling doaj.art-c4f0aa4bf09e4facaa63f1efdc0040de2023-12-03T14:38:38ZengMDPI AGViruses1999-49152022-07-01148162710.3390/v14081627Matrix Metalloproteinases Expression Is Associated with SARS-CoV-2-Induced Lung Pathology and Extracellular-Matrix Remodeling in K18-hACE2 MiceHila Gutman0Moshe Aftalion1Sharon Melamed2Boaz Politi3Reinat Nevo4Sapir Havusha-Laufer5Hagit Achdout6David Gur7Tomer Israely8Shlomit Dachir9Emanuelle Mamroud10Irit Sagi11Yaron Vagima12Israel Institute for Biological Research, Ness Ziona P.O. Box 19, IsraelIsrael Institute for Biological Research, Ness Ziona P.O. Box 19, IsraelIsrael Institute for Biological Research, Ness Ziona P.O. Box 19, IsraelIsrael Institute for Biological Research, Ness Ziona P.O. Box 19, IsraelDepartment of Biomolecular Sciences, Weizmann Institute of Science, Herzel 234, Rehovot P.O. Box 26, IsraelDepartment of Biological Regulation, Weizmann Institute of Science, Herzel 234, Rehovot P.O. Box 26, IsraelIsrael Institute for Biological Research, Ness Ziona P.O. Box 19, IsraelIsrael Institute for Biological Research, Ness Ziona P.O. Box 19, IsraelIsrael Institute for Biological Research, Ness Ziona P.O. Box 19, IsraelIsrael Institute for Biological Research, Ness Ziona P.O. Box 19, IsraelIsrael Institute for Biological Research, Ness Ziona P.O. Box 19, IsraelDepartment of Biological Regulation, Weizmann Institute of Science, Herzel 234, Rehovot P.O. Box 26, IsraelIsrael Institute for Biological Research, Ness Ziona P.O. Box 19, IsraelThe COVID-19 pandemic caused by the SARS-CoV-2 infection induced lung inflammation characterized by cytokine storm and fulminant immune response of both resident and migrated immune cells, accelerating alveolar damage. In this work we identified members of the matrix metalloprotease (MMPs) family associated with lung extra-cellular matrix (ECM) destruction using K18-hACE2-transgenic mice (K18-hACE2) infected intranasally with SARS-CoV-2. Five days post infection, the lungs exhibited overall alveolar damage of epithelial cells and massive leukocytes infiltration. A substantial pulmonary increase in MMP8, MMP9, and MMP14 in the lungs post SARS-CoV-2 infection was associated with degradation of ECM components including collagen, laminin, and proteoglycans. The process of tissue damage and ECM degradation during SARS-CoV-2 lung infection is suggested to be associated with activity of members of the MMPs family, which in turn may be used as a therapeutic intervention.https://www.mdpi.com/1999-4915/14/8/1627COVID-19extra-cellular matrix (ECM)K18-hACE2matrix-metalloproteases (MMP)SARS-CoV-2
spellingShingle Hila Gutman
Moshe Aftalion
Sharon Melamed
Boaz Politi
Reinat Nevo
Sapir Havusha-Laufer
Hagit Achdout
David Gur
Tomer Israely
Shlomit Dachir
Emanuelle Mamroud
Irit Sagi
Yaron Vagima
Matrix Metalloproteinases Expression Is Associated with SARS-CoV-2-Induced Lung Pathology and Extracellular-Matrix Remodeling in K18-hACE2 Mice
Viruses
COVID-19
extra-cellular matrix (ECM)
K18-hACE2
matrix-metalloproteases (MMP)
SARS-CoV-2
title Matrix Metalloproteinases Expression Is Associated with SARS-CoV-2-Induced Lung Pathology and Extracellular-Matrix Remodeling in K18-hACE2 Mice
title_full Matrix Metalloproteinases Expression Is Associated with SARS-CoV-2-Induced Lung Pathology and Extracellular-Matrix Remodeling in K18-hACE2 Mice
title_fullStr Matrix Metalloproteinases Expression Is Associated with SARS-CoV-2-Induced Lung Pathology and Extracellular-Matrix Remodeling in K18-hACE2 Mice
title_full_unstemmed Matrix Metalloproteinases Expression Is Associated with SARS-CoV-2-Induced Lung Pathology and Extracellular-Matrix Remodeling in K18-hACE2 Mice
title_short Matrix Metalloproteinases Expression Is Associated with SARS-CoV-2-Induced Lung Pathology and Extracellular-Matrix Remodeling in K18-hACE2 Mice
title_sort matrix metalloproteinases expression is associated with sars cov 2 induced lung pathology and extracellular matrix remodeling in k18 hace2 mice
topic COVID-19
extra-cellular matrix (ECM)
K18-hACE2
matrix-metalloproteases (MMP)
SARS-CoV-2
url https://www.mdpi.com/1999-4915/14/8/1627
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