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

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 diagno...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8947344/
https://www.ncbi.nlm.nih.gov/pubmed/35326463
http://dx.doi.org/10.3390/cells11061011
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author 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
author_facet 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
author_sort Fassan, Matteo
collection PubMed
description 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.
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spelling pubmed-89473442022-03-25 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 Article 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. MDPI 2022-03-16 /pmc/articles/PMC8947344/ /pubmed/35326463 http://dx.doi.org/10.3390/cells11061011 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
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
Multi-Design Differential Expression Profiling of COVID-19 Lung Autopsy Specimens Reveals Significantly Deregulated Inflammatory Pathways and SFTPC Impaired Transcription
title Multi-Design Differential Expression Profiling of COVID-19 Lung Autopsy Specimens Reveals Significantly Deregulated Inflammatory Pathways and SFTPC Impaired Transcription
title_full Multi-Design Differential Expression Profiling of COVID-19 Lung Autopsy Specimens Reveals Significantly Deregulated Inflammatory Pathways and SFTPC Impaired Transcription
title_fullStr Multi-Design Differential Expression Profiling of COVID-19 Lung Autopsy Specimens Reveals Significantly Deregulated Inflammatory Pathways and SFTPC Impaired Transcription
title_full_unstemmed Multi-Design Differential Expression Profiling of COVID-19 Lung Autopsy Specimens Reveals Significantly Deregulated Inflammatory Pathways and SFTPC Impaired Transcription
title_short Multi-Design Differential Expression Profiling of COVID-19 Lung Autopsy Specimens Reveals Significantly Deregulated Inflammatory Pathways and SFTPC Impaired Transcription
title_sort multi-design differential expression profiling of covid-19 lung autopsy specimens reveals significantly deregulated inflammatory pathways and sftpc impaired transcription
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8947344/
https://www.ncbi.nlm.nih.gov/pubmed/35326463
http://dx.doi.org/10.3390/cells11061011
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