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Lung transcriptome profile of a severe COVID-19 mice model with SARS-CoV-2 spike protein and Poly (I:C)

ABSTRACT: Acute respiratory distress syndrome (ARDS) with COVID-19 is aggravated by hyperinflammatory responses even after the peak of viral load has passed; however, its underlying mechanisms remain unclear. In the present study, analysis of the alveolar tissue injury markers and epithelial cell death markers in patients with COVID-19 revealed that COVID-19-induced ARDS was characterized by alveolar epithelial necrosis at an early disease stage. Serum levels of HMGB-1, one of DAMPs released from necrotic cells, were also significantly elevated in these patients. In addition, we established animal models of COVID-19 by intratracheal instillation with the SARS-CoV-2 spike protein and poly (I:C), a synthetic analog of double-stranded RNA. We performed bioinformatic analysis of lung tissue transcriptomes and confirmed that this COVID-19 model using SARS-CoV-2 spike protein and poly (I:C) recapitulated the biological responses seen in mice infected with SARS-CoV-2. Analysis of the mice model showed that the alveolar epithelial cell necrosis involved two forms of programmed necrosis: necroptosis and pyroptosis, Finally, neutralization of HMGB-1 attenuated alveolar tissue injury in the mouse model. Collectively, necrosis, including necroptosis and pyroptosis, seems to be the predominant form of alveolar epithelial cell death at an early disease stage and subsequent release of DAMPs is a potential driver of COVID-19-induced ARDS.

ORGANISM(S): Mus musculus

PROVIDER: GSE216644 | GEO | 2022/10/31

REPOSITORIES: GEO

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