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

基质金属蛋白酶表达与 SARS-CoV-2 诱发的 K18-hACE2 小鼠肺病理和细胞外基质重塑相关

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作者: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

Abstract

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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