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Downregulation of the Protein C Signaling System Is Associated with COVID-19 Hypercoagulability—A Single-Cell Transcriptomics Analysis

Because of the interface between coagulation and the immune response, it is expected that COVID-19-associated coagulopathy occurs via activated protein C signaling. The objective was to explore putative changes in the expression of the protein C signaling network in the liver, peripheral blood monon...

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Autores principales: Silva, Bruna Rafaela Santos, Jara, Carlos Poblete, Sidarta-Oliveira, Davi, Velloso, Licio A., Velander, William H., Araújo, Eliana P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9785999/
https://www.ncbi.nlm.nih.gov/pubmed/36560757
http://dx.doi.org/10.3390/v14122753
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author Silva, Bruna Rafaela Santos
Jara, Carlos Poblete
Sidarta-Oliveira, Davi
Velloso, Licio A.
Velander, William H.
Araújo, Eliana P.
author_facet Silva, Bruna Rafaela Santos
Jara, Carlos Poblete
Sidarta-Oliveira, Davi
Velloso, Licio A.
Velander, William H.
Araújo, Eliana P.
author_sort Silva, Bruna Rafaela Santos
collection PubMed
description Because of the interface between coagulation and the immune response, it is expected that COVID-19-associated coagulopathy occurs via activated protein C signaling. The objective was to explore putative changes in the expression of the protein C signaling network in the liver, peripheral blood mononuclear cells, and nasal epithelium of patients with COVID-19. Single-cell RNA-sequencing data from patients with COVID-19 and healthy subjects were obtained from the COVID-19 Cell Atlas database. A functional protein–protein interaction network was constructed for the protein C gene. Patients with COVID-19 showed downregulation of protein C and components of the downstream protein C signaling cascade. The percentage of hepatocytes expressing protein C was lower. Part of the liver cell clusters expressing protein C presented increased expression of ACE2. In PBMC, there was increased ACE2, inflammatory, and pro-coagulation transcripts. In the nasal epithelium, PROC, ACE2, and PROS1 were expressed by the ciliated cell cluster, revealing co-expression of ACE-2 with transcripts encoding proteins belonging to the coagulation and immune system interface. Finally, there was upregulation of coagulation factor 3 transcript in the liver and PBMC. Protein C could play a mechanistic role in the hypercoagulability syndrome affecting patients with severe COVID-19.
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spelling pubmed-97859992022-12-24 Downregulation of the Protein C Signaling System Is Associated with COVID-19 Hypercoagulability—A Single-Cell Transcriptomics Analysis Silva, Bruna Rafaela Santos Jara, Carlos Poblete Sidarta-Oliveira, Davi Velloso, Licio A. Velander, William H. Araújo, Eliana P. Viruses Article Because of the interface between coagulation and the immune response, it is expected that COVID-19-associated coagulopathy occurs via activated protein C signaling. The objective was to explore putative changes in the expression of the protein C signaling network in the liver, peripheral blood mononuclear cells, and nasal epithelium of patients with COVID-19. Single-cell RNA-sequencing data from patients with COVID-19 and healthy subjects were obtained from the COVID-19 Cell Atlas database. A functional protein–protein interaction network was constructed for the protein C gene. Patients with COVID-19 showed downregulation of protein C and components of the downstream protein C signaling cascade. The percentage of hepatocytes expressing protein C was lower. Part of the liver cell clusters expressing protein C presented increased expression of ACE2. In PBMC, there was increased ACE2, inflammatory, and pro-coagulation transcripts. In the nasal epithelium, PROC, ACE2, and PROS1 were expressed by the ciliated cell cluster, revealing co-expression of ACE-2 with transcripts encoding proteins belonging to the coagulation and immune system interface. Finally, there was upregulation of coagulation factor 3 transcript in the liver and PBMC. Protein C could play a mechanistic role in the hypercoagulability syndrome affecting patients with severe COVID-19. MDPI 2022-12-09 /pmc/articles/PMC9785999/ /pubmed/36560757 http://dx.doi.org/10.3390/v14122753 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
Silva, Bruna Rafaela Santos
Jara, Carlos Poblete
Sidarta-Oliveira, Davi
Velloso, Licio A.
Velander, William H.
Araújo, Eliana P.
Downregulation of the Protein C Signaling System Is Associated with COVID-19 Hypercoagulability—A Single-Cell Transcriptomics Analysis
title Downregulation of the Protein C Signaling System Is Associated with COVID-19 Hypercoagulability—A Single-Cell Transcriptomics Analysis
title_full Downregulation of the Protein C Signaling System Is Associated with COVID-19 Hypercoagulability—A Single-Cell Transcriptomics Analysis
title_fullStr Downregulation of the Protein C Signaling System Is Associated with COVID-19 Hypercoagulability—A Single-Cell Transcriptomics Analysis
title_full_unstemmed Downregulation of the Protein C Signaling System Is Associated with COVID-19 Hypercoagulability—A Single-Cell Transcriptomics Analysis
title_short Downregulation of the Protein C Signaling System Is Associated with COVID-19 Hypercoagulability—A Single-Cell Transcriptomics Analysis
title_sort downregulation of the protein c signaling system is associated with covid-19 hypercoagulability—a single-cell transcriptomics analysis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9785999/
https://www.ncbi.nlm.nih.gov/pubmed/36560757
http://dx.doi.org/10.3390/v14122753
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