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

Viruses. 2022 Jul 26;14(8):1627. doi: 10.3390/v14081627.

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.

Keywords: COVID-19; K18-hACE2; SARS-CoV-2; extra-cellular matrix (ECM); matrix-metalloproteases (MMP).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin-Converting Enzyme 2
  • Animals
  • COVID-19*
  • Disease Models, Animal
  • Humans
  • Lung / pathology
  • Melphalan
  • Mice
  • Mice, Transgenic
  • Pandemics
  • Peptidyl-Dipeptidase A / metabolism
  • SARS-CoV-2*
  • gamma-Globulins

Substances

  • K-18 conjugate
  • gamma-Globulins
  • Peptidyl-Dipeptidase A
  • Angiotensin-Converting Enzyme 2
  • Melphalan

Grants and funding

This research was funded by the Israel Institute for Biological Research (IIBR), Ness-Ziona, Israel (SB/145). IS an incumbent of the Maurizio Pontecorvo Professorial Chair, and has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (grant agreement No. [695437]), Eu 2020 EDIT consortium, Israeli Science Foundation (1800/19, 1226/13), Thompson Family Foundation.