Modulations of Homeostatic ACE2, CD147, GRP78 Pathways Correlate with Vascular and Endothelial Performance Markers during Pulmonary SARS-CoV-2 Infection
The pathologic consequences of Coronavirus Disease-2019 (COVID-19) include elevated inflammation and dysregulated vascular functions associated with thrombosis. In general, disruption of vascular homeostasis and ensuing prothrombotic events are driven by activated platelets, monocytes, and macrophag...
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MDPI AG
2024-02-01
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| Online Access: | https://www.mdpi.com/2073-4409/13/5/432 |
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| author | Annuurun Nisa Ranjeet Kumar Santhamani Ramasamy Afsal Kolloli Judith Olejnik Sallieu Jalloh Suryaram Gummuluru Selvakumar Subbian Yuri Bushkin |
| author_facet | Annuurun Nisa Ranjeet Kumar Santhamani Ramasamy Afsal Kolloli Judith Olejnik Sallieu Jalloh Suryaram Gummuluru Selvakumar Subbian Yuri Bushkin |
| author_sort | Annuurun Nisa |
| collection | DOAJ |
| description | The pathologic consequences of Coronavirus Disease-2019 (COVID-19) include elevated inflammation and dysregulated vascular functions associated with thrombosis. In general, disruption of vascular homeostasis and ensuing prothrombotic events are driven by activated platelets, monocytes, and macrophages, which form aggregates (thrombi) attached to the endothelium lining of vessel walls. However, molecular pathways underpinning the pathological interactions between myeloid cells and endothelium during COVID-19 remain undefined. Here, we tested the hypothesis that modulations in the expression of cellular receptors angiotensin-converting enzyme 2 (ACE2), CD147, and glucose-regulated protein 78 (GRP78), which are involved in homeostasis and endothelial performance, are the hallmark responses induced by SARS-CoV-2 infection. Cultured macrophages and lungs of hamster model systems were used to test this hypothesis. The results indicate that while macrophages and endothelial cells are less likely to support SARS-CoV-2 proliferation, these cells may readily respond to inflammatory stimuli generated by the infected lung epithelium. SARS-CoV-2 induced modulations of tested cellular receptors correlated with corresponding changes in the mRNA expression of coagulation cascade regulators and endothelial integrity components in infected hamster lungs. Among these markers, tissue factor (TF) had the best correlation for prothrombotic events during SARS-CoV-2 infection. Furthermore, the single-molecule fluorescence in situ hybridization (smFISH) method alone was sufficient to determine the peak and resolution phases of SARS-CoV-2 infection and enabled screening for cellular markers co-expressed with the virus. These findings suggest possible molecular pathways for exploration of novel drugs capable of blocking the prothrombotic shift events that exacerbate COVID-19 pathophysiology and control the disease. |
| first_indexed | 2024-04-25T00:33:03Z |
| format | Article |
| id | doaj.art-1e80c772a02d415e9924b7f035d2985c |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-04-25T00:33:03Z |
| publishDate | 2024-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-1e80c772a02d415e9924b7f035d2985c2024-03-12T16:41:42ZengMDPI AGCells2073-44092024-02-0113543210.3390/cells13050432Modulations of Homeostatic ACE2, CD147, GRP78 Pathways Correlate with Vascular and Endothelial Performance Markers during Pulmonary SARS-CoV-2 InfectionAnnuurun Nisa0Ranjeet Kumar1Santhamani Ramasamy2Afsal Kolloli3Judith Olejnik4Sallieu Jalloh5Suryaram Gummuluru6Selvakumar Subbian7Yuri Bushkin8Public Health Research Institute, New Jersey Medical School, Rutgers University, Newark, NJ 07103, USAPublic Health Research Institute, New Jersey Medical School, Rutgers University, Newark, NJ 07103, USAPublic Health Research Institute, New Jersey Medical School, Rutgers University, Newark, NJ 07103, USAPublic Health Research Institute, New Jersey Medical School, Rutgers University, Newark, NJ 07103, USADepartment of Virology, Immunology & Microbiology, Boston University School of Medicine, Boston, MA 02130, USADepartment of Virology, Immunology & Microbiology, Boston University School of Medicine, Boston, MA 02130, USADepartment of Virology, Immunology & Microbiology, Boston University School of Medicine, Boston, MA 02130, USAPublic Health Research Institute, New Jersey Medical School, Rutgers University, Newark, NJ 07103, USAPublic Health Research Institute, New Jersey Medical School, Rutgers University, Newark, NJ 07103, USAThe pathologic consequences of Coronavirus Disease-2019 (COVID-19) include elevated inflammation and dysregulated vascular functions associated with thrombosis. In general, disruption of vascular homeostasis and ensuing prothrombotic events are driven by activated platelets, monocytes, and macrophages, which form aggregates (thrombi) attached to the endothelium lining of vessel walls. However, molecular pathways underpinning the pathological interactions between myeloid cells and endothelium during COVID-19 remain undefined. Here, we tested the hypothesis that modulations in the expression of cellular receptors angiotensin-converting enzyme 2 (ACE2), CD147, and glucose-regulated protein 78 (GRP78), which are involved in homeostasis and endothelial performance, are the hallmark responses induced by SARS-CoV-2 infection. Cultured macrophages and lungs of hamster model systems were used to test this hypothesis. The results indicate that while macrophages and endothelial cells are less likely to support SARS-CoV-2 proliferation, these cells may readily respond to inflammatory stimuli generated by the infected lung epithelium. SARS-CoV-2 induced modulations of tested cellular receptors correlated with corresponding changes in the mRNA expression of coagulation cascade regulators and endothelial integrity components in infected hamster lungs. Among these markers, tissue factor (TF) had the best correlation for prothrombotic events during SARS-CoV-2 infection. Furthermore, the single-molecule fluorescence in situ hybridization (smFISH) method alone was sufficient to determine the peak and resolution phases of SARS-CoV-2 infection and enabled screening for cellular markers co-expressed with the virus. These findings suggest possible molecular pathways for exploration of novel drugs capable of blocking the prothrombotic shift events that exacerbate COVID-19 pathophysiology and control the disease.https://www.mdpi.com/2073-4409/13/5/432COVID-19ACE2CD147GRP78single-molecule FISHthrombosis |
| spellingShingle | Annuurun Nisa Ranjeet Kumar Santhamani Ramasamy Afsal Kolloli Judith Olejnik Sallieu Jalloh Suryaram Gummuluru Selvakumar Subbian Yuri Bushkin Modulations of Homeostatic ACE2, CD147, GRP78 Pathways Correlate with Vascular and Endothelial Performance Markers during Pulmonary SARS-CoV-2 Infection Cells COVID-19 ACE2 CD147 GRP78 single-molecule FISH thrombosis |
| title | Modulations of Homeostatic ACE2, CD147, GRP78 Pathways Correlate with Vascular and Endothelial Performance Markers during Pulmonary SARS-CoV-2 Infection |
| title_full | Modulations of Homeostatic ACE2, CD147, GRP78 Pathways Correlate with Vascular and Endothelial Performance Markers during Pulmonary SARS-CoV-2 Infection |
| title_fullStr | Modulations of Homeostatic ACE2, CD147, GRP78 Pathways Correlate with Vascular and Endothelial Performance Markers during Pulmonary SARS-CoV-2 Infection |
| title_full_unstemmed | Modulations of Homeostatic ACE2, CD147, GRP78 Pathways Correlate with Vascular and Endothelial Performance Markers during Pulmonary SARS-CoV-2 Infection |
| title_short | Modulations of Homeostatic ACE2, CD147, GRP78 Pathways Correlate with Vascular and Endothelial Performance Markers during Pulmonary SARS-CoV-2 Infection |
| title_sort | modulations of homeostatic ace2 cd147 grp78 pathways correlate with vascular and endothelial performance markers during pulmonary sars cov 2 infection |
| topic | COVID-19 ACE2 CD147 GRP78 single-molecule FISH thrombosis |
| url | https://www.mdpi.com/2073-4409/13/5/432 |
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