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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| Format: | Article |
| Language: | English |
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MDPI AG
2022-12-01
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| Series: | Viruses |
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| Online Access: | https://www.mdpi.com/1999-4915/14/12/2753 |
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| author | Bruna Rafaela Santos Silva Carlos Poblete Jara Davi Sidarta-Oliveira Licio A. Velloso William H. Velander Eliana P. Araújo |
| author_facet | Bruna Rafaela Santos Silva Carlos Poblete Jara Davi Sidarta-Oliveira Licio A. Velloso William H. Velander Eliana P. Araújo |
| author_sort | Bruna Rafaela Santos Silva |
| collection | DOAJ |
| 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 <i>ACE2</i>. In PBMC, there was increased <i>ACE2</i>, inflammatory, and pro-coagulation transcripts. In the nasal epithelium, <i>PROC</i>, <i>ACE2,</i> and <i>PROS1</i> 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. |
| first_indexed | 2024-03-09T15:44:34Z |
| format | Article |
| id | doaj.art-390da805d08c4b968d9e8b9c91d25e69 |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-09T15:44:34Z |
| publishDate | 2022-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-390da805d08c4b968d9e8b9c91d25e692023-11-24T18:39:03ZengMDPI AGViruses1999-49152022-12-011412275310.3390/v14122753Downregulation of the Protein C Signaling System Is Associated with COVID-19 Hypercoagulability—A Single-Cell Transcriptomics AnalysisBruna Rafaela Santos Silva0Carlos Poblete Jara1Davi Sidarta-Oliveira2Licio A. Velloso3William H. Velander4Eliana P. Araújo5Nursing School, University of Campinas, Tessalia Vieira de Camargo, 126, Campinas 13084-970, BrazilDepartment of Chemical and Biomolecular Engineering, University of Nebraska, Lincoln, NE 68588-0643, USALaboratory of Cell Signalling, Obesity and Comorbidities Center, OCRC, University of Campinas, Carl Von Linnaeus, s/n, Campinas 13084-864, BrazilLaboratory of Cell Signalling, Obesity and Comorbidities Center, OCRC, University of Campinas, Carl Von Linnaeus, s/n, Campinas 13084-864, BrazilDepartment of Chemical and Biomolecular Engineering, University of Nebraska, Lincoln, NE 68588-0643, USANursing School, University of Campinas, Tessalia Vieira de Camargo, 126, Campinas 13084-970, BrazilBecause 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 <i>ACE2</i>. In PBMC, there was increased <i>ACE2</i>, inflammatory, and pro-coagulation transcripts. In the nasal epithelium, <i>PROC</i>, <i>ACE2,</i> and <i>PROS1</i> 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.https://www.mdpi.com/1999-4915/14/12/2753antigen-presenting cellcomputational biologyblood coagulation disordersendothelial cellsSARS-CoV-2 |
| spellingShingle | Bruna Rafaela Santos Silva Carlos Poblete Jara Davi Sidarta-Oliveira Licio A. Velloso William H. Velander Eliana P. Araújo Downregulation of the Protein C Signaling System Is Associated with COVID-19 Hypercoagulability—A Single-Cell Transcriptomics Analysis Viruses antigen-presenting cell computational biology blood coagulation disorders endothelial cells SARS-CoV-2 |
| 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 | antigen-presenting cell computational biology blood coagulation disorders endothelial cells SARS-CoV-2 |
| url | https://www.mdpi.com/1999-4915/14/12/2753 |
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