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Angiotensin-converting Enzyme-2 (ACE2) Expression in Pediatric Liver Disease.
James P Stevens1,2, Vasantha L Kolachala1, Gaurav N Joshi3
1Department of Pediatrics, Emory University School of Medicine.
Applied Immunohistochemistry & Molecular Morphology : AIMM
|October 12, 2022
Summary
Angiotensin-converting enzyme-2 (ACE2) is found in the liver, particularly on cholangiocytes. Pediatric liver disease patients show increased hepatic ACE2 expression compared to controls.
Area of Science:
- Hepatology and Immunology
- Molecular Biology and Virology
Background:
- Angiotensin-converting enzyme-2 (ACE2) is a known receptor for SARS-CoV-2.
- ACE2 expression in the liver is documented but its precise function remains unclear.
- Understanding ACE2 in liver disease is crucial given its role in infections like COVID-19.
Purpose of the Study:
- To assess ACE2 expression in pediatric immune-mediated liver disease using novel methods.
- To investigate the localization and quantification of ACE2 within liver tissue.
- To explore the role of ACE2 in liver diseases and during viral infections.
Main Methods:
- Immunofluorescent staining of liver tissue for ACE2, analyzed by confocal microscopy.
- Deep learning-based segmentation for quantifying cellular ACE2 expression.
- Spatial transcriptomics for high-throughput gene expression and cellular composition analysis.
- Enzyme-linked immunosorbent assay (ELISA) for quantifying plasma ACE2 levels.
Main Results:
- High ACE2 expression was observed on the apical surface of cholangiocytes, with lower levels in hepatocytes and nonparenchymal cells.
- Pediatric patients with liver disease exhibited significantly higher hepatic ACE2 expression than healthy pediatric controls.
- Adult control liver tissue showed higher ACE2 expression compared to pediatric controls.
- No statistically significant difference in plasma ACE2 levels was detected between groups.
- Spatial transcriptomics identified antibody-secreting cells within ACE2-expressing regions.
Conclusions:
- ACE2 is expressed throughout the liver, predominantly on cholangiocyte membranes.
- Machine learning effectively identifies hepatic cellular components for histological analysis.
- Hepatic ACE2 expression may be elevated in pediatric liver disease.
- Further research is required to elucidate ACE2's role in chronic liver conditions and acute infections.
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