
This AOP is licensed under a Creative Commons Attribution 4.0 International License.
Aop: 428
Title
Binding of S-protein to ACE2 in enterocytes induces ACE2 dysregulation leading to gut dysbiosis
Short name
Graphical Representation
Point of Contact
Contributors
- Laure-Alix Clerbaux
- Julija Filipovska
Status
Author status | OECD status | OECD project | SAAOP status |
---|---|---|---|
Under development: Not open for comment. Do not cite | Under Development | 1.96 | Included in OECD Work Plan |
This AOP was last modified on December 07, 2022 04:57
Revision dates for related pages
Page | Revision Date/Time |
---|---|
Binding to ACE2 | May 17, 2022 10:20 |
Dysregulation, ACE2 expression and activity | February 18, 2023 12:20 |
Gut microbiota, alteration | January 04, 2022 10:31 |
Binding to ACE2 leads to ACE2 dysregulation | February 07, 2023 23:35 |
ACE2 dysregulation leads to Gut dysbiosis | December 02, 2021 07:16 |
Abstract
S-protein binding to ACE2 receptor induces dysregulation of ACE2 physiological functions in the intestines such as modulation of the local renin-angiotensin signaling (RAS) system (10.1152/ajpgi.00099.202) or as a chaperone for dietary amino acid (AA) transporters in the intestines, such as the tryptophan transporter B0AT1 (Slc6a19) (10.1042/CS20200477; 10.1053/j.gastro.2008.10.055). The gastrointestinal RAS appears to be involved in numerous processes in the gut including AA, fluid and electrolyte absorption and secretion (10.1111/j.1365-2036.2011.04971.x.). Besides, the gut microbiota is influenced by the host intestinal AA metabolism as gut bacteria use dietary AA for protein synthesis (10.1038/s41598-020-74122-9).
AOP Development Strategy
Context
AOP428 has been developed within the CIAO project - "Modelling the Pathogenesis of COVID-19 Using the Adverse Outcome Pathway (AOP)". The overall goal is to organize the vast amount of data that is constantly evolving as a result of the COVID-19 pandemic and identify uncertainties and knowledge gaps that may be missing using the AOP framework. Many AOPs were developed in the CIAO project, each AOP focusing on a specific element of the SARS-COV-2 virus responses in humans.
AOP428 focuses on the alteration of the gut microbiota via ACE2 dysregulation in the gut.
Strategy
Summary of the AOP
Events:
Molecular Initiating Events (MIE)
Key Events (KE)
Adverse Outcomes (AO)
Type | Event ID | Title | Short name |
---|
MIE | 1739 | Binding to ACE2 | Binding to ACE2 |
KE | 1854 | Dysregulation, ACE2 expression and activity | ACE2 dysregulation |
KE | 1954 | Gut microbiota, alteration | Gut dysbiosis |
Relationships Between Two Key Events (Including MIEs and AOs)
Title | Adjacency | Evidence | Quantitative Understanding |
---|
Binding to ACE2 leads to ACE2 dysregulation | adjacent | Moderate | |
ACE2 dysregulation leads to Gut dysbiosis | adjacent | Moderate | Moderate |
Network View
Prototypical Stressors
Life Stage Applicability
Taxonomic Applicability
Sex Applicability
Overall Assessment of the AOP
Domain of Applicability
Essentiality of the Key Events
Evidence Assessment
Known Modulating Factors
Modulating Factor (MF) | Influence or Outcome | KER(s) involved |
---|---|---|