40% of severe acute respiratory syndrome coronavirus two (SARS-CoV-2)
severe cases develop acute kidney injury (AKI). Current treatment for renal
complications limits financial and material resources available. To explore alternative
treatments and accelerate research in case of future coronavirus outbreaks, a mouse
model of coronavirus disease 2019-associated AKI (C19-AKI) would represent a
critical biomedical research tool. The surrogate model of C19-AKI (SMC) developed
consisted of angiotensin-converting enzyme two (ACE2) knockout (KO) mice receiving
400 ng/kg/min of angiotensin (Ang) II by osmotic minipump for eight days with a single
injection of lipopolysaccharide (LPS; 10 mg/kg) on the seventh day of Ang II and
euthanasia 24 hours after LPS. Similarly, to C19-AKI, the SMC exhibited albuminuria,
elevated blood urea nitrogen, electrolyte imbalance, neutrophil infiltration, and
upregulation of the G-coupled protein receptor (GPR)84 and pro-inflammatory and
injury markers. GPR84 was found in bronchoalveolar lavage fluid neutrophils of
coronavirus disease 2019 (COVID-19) patients, suggesting a potential implication of
GPR84 in the disease. We hypothesised that GPR84 deletion or antagonism with
GLPG-1205 could attenuate SMC’s indices of renal injury and inflammation. GLPG-1205 and GPR84 KO had no effects in the SMC model, as suggested by unchanged
albuminuria, electrolytes, and markers expression. Interestingly, neutrophil infiltration
was attenuated by GLPG-1205 only. The SMC is an interesting tool for therapeutic
development for infections associated with renal injury, such as SARS-CoV-2. GPR84
role in the SMC needs to be further assessed.
| Identifer | oai:union.ndltd.org:uottawa.ca/oai:ruor.uottawa.ca:10393/44466 |
| Date | 05 January 2023 |
| Creators | Blais, Amélie |
| Contributors | Kennedy, Christopher Rode |
| Publisher | Université d'Ottawa / University of Ottawa |
| Source Sets | Université d’Ottawa |
| Language | English |
| Detected Language | English |
| Type | Thesis |
| Format | application/pdf |
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