Journal
BIOMOLECULES
Volume 12, Issue 5, Pages -Publisher
MDPI
DOI: 10.3390/biom12050604
Keywords
metalloproteinases; sHLA-G; sTREM-1; lipid peroxidation; COVID-19
Categories
Funding
- Fundacao de Amparo a Pesquisa do Estado de Sao PauloFAPESP [2020/05207-6, 2014/07125-6, 2020/08534-8, 2020/05270-0, 2014/23946-0, 2021/04590-3]
- Coordination for the Improvement of Higher Educational Personnel (CAPES) [001]
- Fundacao de apoio a Universidade de Sao Paulo-FUSP by USP VIDA program
- Fundacao de Amparo a Pesquisa do Estado do Amazonas-FAPEAM [006/2020]
- Conselho Nacional de Desenvolvimento Cientifico e Tecnologico CNPq [312606/2019-2, 303259/2020-5, 309583/2019-5, 314358/2021-8]
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This study found that excessive activity of matrix metalloproteinases (MMPs) contributes to extensive lung tissue damage in severe COVID-19. MMP-2 and MMP-8 play important roles in this process and are associated with the release of immunosuppressive mediators sHLA-G and sTREM-1.
Patients with COVID-19 predominantly have a respiratory tract infection and acute lung failure is the most severe complication. While the molecular basis of SARS-CoV-2 immunopathology is still unknown, it is well established that lung infection is associated with hyper-inflammation and tissue damage. Matrix metalloproteinases (MMPs) contribute to tissue destruction in many pathological situations, and the activity of MMPs in the lung leads to the release of bioactive mediators with inflammatory properties. We sought to characterize a scenario in which MMPs could influence the lung pathogenesis of COVID-19. Although we observed high diversity of MMPs in lung tissue from COVID-19 patients by proteomics, we specified the expression and enzyme activity of MMP-2 in tracheal-aspirate fluid (TAF) samples from intubated COVID-19 and non-COVID-19 patients. Moreover, the expression of MMP-8 was positively correlated with MMP-2 levels and possible shedding of the immunosuppression mediator sHLA-G and sTREM-1. Together, overexpression of the MMP-2/MMP-8 axis, in addition to neutrophil infiltration and products, such as reactive oxygen species (ROS), increased lipid peroxidation that could promote intensive destruction of lung tissue in severe COVID-19. Thus, the inhibition of MMPs can be a novel target and promising treatment strategy in severe COVID-19.
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