Ephrin-A1 and the sheddase ADAM12 are upregulated in COVID-19
More than 3.5 million people have died globally from COVID-19, yet an effective therapy is not available. It is, therefore, important to understand the signaling pathways that mediate disease progression in order to identify new molecular targets for therapeutic development. Here, we report that the...
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doaj-5aa908018b37400f925542e5d5f223a22021-07-05T16:34:14ZengElsevierHeliyon2405-84402021-06-0176e07200Ephrin-A1 and the sheddase ADAM12 are upregulated in COVID-19Rachelle Mendoza0Nayanendu Saha1Amir Momeni2Elmer Gabutan3Mouyed Alawad4Amir Dehghani5John Diks6Bo Lin7Donghai Wang8Mohamed Alshal9William Fyke10Bingcheng Wang11Juha P. Himanen12Prem Premsrirut13Dimitar B. Nikolov14Department of Pathology, SUNY Downstate Health Sciences University, 450 Clarkson Avenue, Brooklyn, NY 11203, USAStructural Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USABrigham and Women's Hospital, 75 Francis St, Boston, MA 02115, USADepartment of Pathology, SUNY Downstate Health Sciences University, 450 Clarkson Avenue, Brooklyn, NY 11203, USADepartment of Pathology, SUNY Downstate Health Sciences University, 450 Clarkson Avenue, Brooklyn, NY 11203, USADepartment of Pathology, SUNY Downstate Health Sciences University, 450 Clarkson Avenue, Brooklyn, NY 11203, USADepartment of Pathology, SUNY Downstate Health Sciences University, 450 Clarkson Avenue, Brooklyn, NY 11203, USADepartment of Pathology, SUNY Downstate Health Sciences University, 450 Clarkson Avenue, Brooklyn, NY 11203, USADepartment of Pathology, SUNY Downstate Health Sciences University, 450 Clarkson Avenue, Brooklyn, NY 11203, USADepartment of Pathology, SUNY Downstate Health Sciences University, 450 Clarkson Avenue, Brooklyn, NY 11203, USADepartment of Pathology, SUNY Downstate Health Sciences University, 450 Clarkson Avenue, Brooklyn, NY 11203, USARammelkamp Center for Research, Department of Medicine, MetroHealth Medical Center, 2500 MetroHealth Drive, Cleveland, Ohio 44109, USAStructural Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USADepartment of Cell Biology, SUNY Downstate Health Sciences University, 450 Clarkson Avenue, Brooklyn, NY 11203, USA; Mirimus Inc., 760 Parkside Ave, Brooklyn, NY 11226, USAStructural Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Corresponding author.More than 3.5 million people have died globally from COVID-19, yet an effective therapy is not available. It is, therefore, important to understand the signaling pathways that mediate disease progression in order to identify new molecular targets for therapeutic development. Here, we report that the blood serum levels of ephrin-A1 and the sheddase ADAM12 were significantly elevated in COVID-19 patients treated at SUNY Downstate Hospital of Brooklyn, New York. Both ephrin-A1 and ADAM12 are known to be involved in inflammation and regulate endothelial cell permeability, thus providing a gateway to lung injury. The clinical outcome correlated with the ephrin-A1 and ADAM12 serum levels during the first week of hospitalization. In contrast, the serum levels of TNFα were elevated in only a small subset of the patients, and these same patients also had highly elevated levels of the sheddase ADAM17. These data indicate that ephrin-A1-mediated inflammatory signaling may contribute to COVID-19 disease progression more so than TNFα-mediated inflammatory signaling. They also support the notion that, in COVID-19 inflammation, ADAM12 sheds ephrin-A1, while ADAM17 sheds TNFα. Furthermore, the results suggest that elevated serum levels and activity of cytokines, such as TNFα, and other secreted inflammatory molecules, such as ephrin-A1, are not simply due to overexpression, but also to upregulation of sheddases that release them into the blood circulation. Our results identify ephrin-A1, ADAM12, and other molecules in the ephrin-A1 signaling pathway as potential pharmacological targets for treating COVID-19 inflammation.http://www.sciencedirect.com/science/article/pii/S2405844021013037COVID-19InflammationEphrinEph receptorsADAM proteases |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Rachelle Mendoza Nayanendu Saha Amir Momeni Elmer Gabutan Mouyed Alawad Amir Dehghani John Diks Bo Lin Donghai Wang Mohamed Alshal William Fyke Bingcheng Wang Juha P. Himanen Prem Premsrirut Dimitar B. Nikolov |
spellingShingle |
Rachelle Mendoza Nayanendu Saha Amir Momeni Elmer Gabutan Mouyed Alawad Amir Dehghani John Diks Bo Lin Donghai Wang Mohamed Alshal William Fyke Bingcheng Wang Juha P. Himanen Prem Premsrirut Dimitar B. Nikolov Ephrin-A1 and the sheddase ADAM12 are upregulated in COVID-19 Heliyon COVID-19 Inflammation Ephrin Eph receptors ADAM proteases |
author_facet |
Rachelle Mendoza Nayanendu Saha Amir Momeni Elmer Gabutan Mouyed Alawad Amir Dehghani John Diks Bo Lin Donghai Wang Mohamed Alshal William Fyke Bingcheng Wang Juha P. Himanen Prem Premsrirut Dimitar B. Nikolov |
author_sort |
Rachelle Mendoza |
title |
Ephrin-A1 and the sheddase ADAM12 are upregulated in COVID-19 |
title_short |
Ephrin-A1 and the sheddase ADAM12 are upregulated in COVID-19 |
title_full |
Ephrin-A1 and the sheddase ADAM12 are upregulated in COVID-19 |
title_fullStr |
Ephrin-A1 and the sheddase ADAM12 are upregulated in COVID-19 |
title_full_unstemmed |
Ephrin-A1 and the sheddase ADAM12 are upregulated in COVID-19 |
title_sort |
ephrin-a1 and the sheddase adam12 are upregulated in covid-19 |
publisher |
Elsevier |
series |
Heliyon |
issn |
2405-8440 |
publishDate |
2021-06-01 |
description |
More than 3.5 million people have died globally from COVID-19, yet an effective therapy is not available. It is, therefore, important to understand the signaling pathways that mediate disease progression in order to identify new molecular targets for therapeutic development. Here, we report that the blood serum levels of ephrin-A1 and the sheddase ADAM12 were significantly elevated in COVID-19 patients treated at SUNY Downstate Hospital of Brooklyn, New York. Both ephrin-A1 and ADAM12 are known to be involved in inflammation and regulate endothelial cell permeability, thus providing a gateway to lung injury. The clinical outcome correlated with the ephrin-A1 and ADAM12 serum levels during the first week of hospitalization. In contrast, the serum levels of TNFα were elevated in only a small subset of the patients, and these same patients also had highly elevated levels of the sheddase ADAM17. These data indicate that ephrin-A1-mediated inflammatory signaling may contribute to COVID-19 disease progression more so than TNFα-mediated inflammatory signaling. They also support the notion that, in COVID-19 inflammation, ADAM12 sheds ephrin-A1, while ADAM17 sheds TNFα. Furthermore, the results suggest that elevated serum levels and activity of cytokines, such as TNFα, and other secreted inflammatory molecules, such as ephrin-A1, are not simply due to overexpression, but also to upregulation of sheddases that release them into the blood circulation. Our results identify ephrin-A1, ADAM12, and other molecules in the ephrin-A1 signaling pathway as potential pharmacological targets for treating COVID-19 inflammation. |
topic |
COVID-19 Inflammation Ephrin Eph receptors ADAM proteases |
url |
http://www.sciencedirect.com/science/article/pii/S2405844021013037 |
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