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Multi-Design Differential Expression Profiling of COVID-19 Lung Autopsy Specimens Reveals Significantly Deregulated Inflammatory Pathways and SFTPC Impaired Transcription

Fassan, Matteo ; Collesei, Antonio ; Angerilli, Valentina ; Sbaraglia, Marta ; Fortarezza, Francesco ; Pezzuto, Federica ; De Gaspari, Monica ; Businello, Gianluca ; Moni, Margherita ; Rizzo, Stefania ; Traverso, Giulia ; Colosso, Veronica ; Taschin, Elisa ; Lunardi, Francesca ; Valls, Aida Freire ; Schiavi, Francesca ; Basso, Cristina ; Calabrese, Fiorella ; Dei Tos, Angelo Paolo

Cells (Basel, Switzerland), 2022-03, Vol.11 (6), p.1011 [Periódico revisado por pares]

Switzerland: MDPI AG

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Título:
Multi-Design Differential Expression Profiling of COVID-19 Lung Autopsy Specimens Reveals Significantly Deregulated Inflammatory Pathways and SFTPC Impaired Transcription
Autor: Fassan, Matteo ; Collesei, Antonio ; Angerilli, Valentina ; Sbaraglia, Marta ; Fortarezza, Francesco ; Pezzuto, Federica ; De Gaspari, Monica ; Businello, Gianluca ; Moni, Margherita ; Rizzo, Stefania ; Traverso, Giulia ; Colosso, Veronica ; Taschin, Elisa ; Lunardi, Francesca ; Valls, Aida Freire ; Schiavi, Francesca ; Basso, Cristina ; Calabrese, Fiorella ; Dei Tos, Angelo Paolo
Assuntos: Autopsies ; Autopsy ; Cathepsin C ; CD163 antigen ; Cell activation ; complement ; Complement activation ; Complement component C2 ; Coronaviruses ; COVID-19 ; COVID-19 - genetics ; Dipeptidyl-peptidase I ; Edema ; Gene expression ; Humans ; Immune system ; Immunohistochemistry ; Infections ; Inflammation ; Interferon ; Lung - pathology ; Lungs ; Macrophages ; Metadata ; Paraffin ; Pathology ; Pneumonia ; Protein C ; Pulmonary Surfactant-Associated Protein C ; Respiratory diseases ; SARS-CoV-2 ; Severe acute respiratory syndrome coronavirus 2 ; Signal transduction ; Software ; Surfactant protein C ; Therapeutic targets ; Transcription ; transcriptomic profiling ; Transcriptomics ; Viral infections
É parte de: Cells (Basel, Switzerland), 2022-03, Vol.11 (6), p.1011
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
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These authors contributed equally to this work as first author.
These authors contributed equally to this work as last author.
Descrição: The transcriptomic profiling of lung damage associated with SARS-CoV-2 infection may lead to the development of effective therapies to prevent COVID-19-related deaths. We selected a series of 21 autoptic lung samples, 14 of which had positive nasopharyngeal swabs for SARS-CoV-2 and a clinical diagnosis of COVID-19-related death; their pulmonary viral load was quantified with a specific probe for SARS-CoV-2. The remaining seven cases had no documented respiratory disease and were used as controls. RNA from formalin-fixed paraffin-embedded (FFPE) tissue samples was extracted to perform gene expression profiling by means of targeted (Nanostring) and comprehensive RNA-Seq. Two differential expression designs were carried out leading to relevant results in terms of deregulation. SARS-CoV-2 positive specimens presented a significant overexpression in genes of the type I interferon signaling pathway (IFIT1, OAS1, ISG15 and RSAD2), complement activation (C2 and CFB), macrophage polarization (PKM, SIGLEC1, CD163 and MS4A4A) and Cathepsin C (CTSC). CD163, Siglec-1 and Cathepsin C overexpression was validated by immunohistochemistry. SFTPC, the encoding gene for pulmonary-associated surfactant protein C, emerged as a key identifier of COVID-19 patients with high viral load. This study successfully recognized SARS-CoV-2 specific immune signatures in lung samples and highlighted new potential therapeutic targets. A better understanding of the immunopathogenic mechanisms of SARS-CoV-2 induced lung damage is required to develop effective individualized pharmacological strategies.
Editor: Switzerland: MDPI AG
Idioma: Inglês

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Multi-Design Differential Expression Profiling of COVID-19 Lung Autopsy Specimens Reveals Significantly Deregulated Inflammatory Pathways and SFTPC Impaired Transcription

Switzerland: MDPI AG

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