Cargando…
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...
Autores principales: | , , , , , |
---|---|
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 |
_version_ | 1784858185538994176 |
---|---|
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. |
format | Online Article Text |
id | pubmed-9785999 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT silvabrunarafaelasantos downregulationoftheproteincsignalingsystemisassociatedwithcovid19hypercoagulabilityasinglecelltranscriptomicsanalysis AT jaracarlospoblete downregulationoftheproteincsignalingsystemisassociatedwithcovid19hypercoagulabilityasinglecelltranscriptomicsanalysis AT sidartaoliveiradavi downregulationoftheproteincsignalingsystemisassociatedwithcovid19hypercoagulabilityasinglecelltranscriptomicsanalysis AT vellosolicioa downregulationoftheproteincsignalingsystemisassociatedwithcovid19hypercoagulabilityasinglecelltranscriptomicsanalysis AT velanderwilliamh downregulationoftheproteincsignalingsystemisassociatedwithcovid19hypercoagulabilityasinglecelltranscriptomicsanalysis AT araujoelianap downregulationoftheproteincsignalingsystemisassociatedwithcovid19hypercoagulabilityasinglecelltranscriptomicsanalysis |