NOTCH signaling in COVID-19: a central hub controlling genes, proteins, and cells that mediate SARS-CoV-2 entry, the inflammatory response, and lung regeneration.
ACE2
ADAM
COVID-19
Notch
SARS-CoV-2
furin
gamma-secretase inhibitor (GSI)
Journal
Frontiers in cellular and infection microbiology
ISSN: 2235-2988
Titre abrégé: Front Cell Infect Microbiol
Pays: Switzerland
ID NLM: 101585359
Informations de publication
Date de publication:
2022
2022
Historique:
received:
26
04
2022
accepted:
11
07
2022
entrez:
22
8
2022
pubmed:
23
8
2022
medline:
24
8
2022
Statut:
epublish
Résumé
In the lungs of infected individuals, the downstream molecular signaling pathways induced by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) are incompletely understood. Here, we describe and examine predictions of a model in which NOTCH may represent a central signaling axis in lung infection in Coronavirus Disease 2019 (COVID-19). A pathway involving NOTCH signaling, furin, ADAM17, and ACE2 may be capable of increasing SARS-CoV-2 viral entry and infection. NOTCH signaling can also upregulate IL-6 and pro-inflammatory mediators induced to hyperactivation in COVID-19. Furthermore, if NOTCH signaling fails to turn down properly and stays elevated, airway regeneration during lung healing can be inhibited-a process that may be at play in COVID-19. With specific NOTCH inhibitor drugs in development and clinical trials for other diseases being conducted, the roles of NOTCH in all of these processes central to both infection and healing merit contemplation if such drugs might be applied to COVID-19 patients.
Identifiants
pubmed: 35992174
doi: 10.3389/fcimb.2022.928704
pmc: PMC9386183
doi:
Substances chimiques
Peptidyl-Dipeptidase A
EC 3.4.15.1
Angiotensin-Converting Enzyme 2
EC 3.4.17.23
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
928704Subventions
Organisme : NIGMS NIH HHS
ID : R01 GM103841
Pays : United States
Informations de copyright
Copyright © 2022 Baindara, Sarker, Earhart, Mandal and Schrum.
Déclaration de conflit d'intérêts
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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