The SARS-CoV-2 receptor and other key components of the Renin-Angiotensin-Aldosterone System related to COVID-19 are expressed in enterocytes in larval zebrafish
| Autor: | Karen Guillemin, John H. Postlethwait, Michelle S. Massaquoi, Adam C. Miller, Yi-Lin Yan, Dylan R. Farnsworth |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Cell type
animal structures QH301-705.5 Science medicine.disease_cause General Biochemistry Genetics and Molecular Biology Renin-Angiotensin System scrna-seq 03 medical and health sciences 0302 clinical medicine Renin–angiotensin system genome duplication medicine Animals Humans Biology (General) Receptor Zebrafish 030304 developmental biology Coronavirus Apelin receptor 0303 health sciences biology SARS-CoV-2 Methods & Techniques fungi Zebrafish Proteins biology.organism_classification Angiotensin II Apelin Cell biology Disease Models Animal Enterocytes Gene Expression Regulation apelin covid-19 danio rerio conserved synteny General Agricultural and Biological Sciences 030217 neurology & neurosurgery |
| Zdroj: | Biology Open, Vol 10, Iss 3 (2021) Biology Open article-version (VoR) Version of Record |
| ISSN: | 2046-6390 |
| Popis: | People with underlying conditions, including hypertension, obesity, and diabetes, are especially susceptible to negative outcomes after infection with coronavirus SARS-CoV-2, which causes COVID-19. Hypertension and respiratory inflammation are exacerbated by the Renin-Angiotensin-Aldosterone System (RAAS), which normally protects from rapidly dropping blood pressure via Angiotensin II (Ang II) produced by the enzyme Ace. The Ace paralog Ace2 degrades Ang II, counteracting its chronic effects, and serves as the SARS-CoV-2 receptor. Ace, the coronavirus, and COVID-19 comorbidities all regulate Ace2, but we do not yet understand how. To exploit zebrafish (Danio rerio) to help understand the relationship of the RAAS to COVID-19, we must identify zebrafish orthologs and co-orthologs of human RAAS genes and understand their expression patterns. To achieve these goals, we conducted genomic and phylogenetic analyses and investigated single cell transcriptomes. Results showed that most human RAAS genes have one or more zebrafish orthologs or co-orthologs. Results identified a specific type of enterocyte as the specific site of expression of zebrafish orthologs of key RAAS components, including Ace, Ace2, Slc6a19 (SARS-CoV-2 co-receptor), and the Angiotensin-related peptide cleaving enzymes Anpep (receptor for the common cold coronavirus HCoV-229E), and Dpp4 (receptor for the Middle East Respiratory Syndrome virus, MERS-CoV). Results identified specific vascular cell subtypes expressing Ang II receptors, apelin, and apelin receptor genes. These results identify genes and cell types to exploit zebrafish as a disease model for understanding mechanisms of COVID-19. Summary: Genomic analyses identify zebrafish orthologs of the Renin-Angiotensin-Aldosterone System that contribute to COVID-19 comorbidities and single-cell transcriptomics shows that they act in a specialized intestinal cell type. |
| Databáze: | OpenAIRE |
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