Specific ACE2 Expression in Cholangiocytes May Cause Liver Damage After 2019-nCoV Infection
Open accessAbstract
A newly identified coronavirus, 2019-nCoV, has been posing significant threats to public health since December 2019. ACE2, the host cell receptor for severe acute respiratory syndrome coronavirus (SARS), has recently been demonstrated in mediating 2019-nCoV infection. Interestingly, besides the respiratory system, substantial proportion of SARS and 2019-nCoV patients showed signs of various degrees of liver damage, the mechanism and implication of which have not yet been determined. Here, we performed an unbiased evaluation of cell type specific expression of ACE2 in healthy liver tissues using single cell RNA-seq data of two independent cohorts, and identified specific expression in cholangiocytes. The results indicated that virus might directly bind to ACE2 positive cholangiocytes but not necessarily hepatocytes. This finding suggested the liver abnormalities of SARS and 2019-nCoV patients may not be due to hepatocyte damage, but cholangiocyte dysfunction and other causes such as drug induced and systemic inflammatory response induced liver injury. Our findings indicate that special care of liver dysfunction should be installed in treating 2019-nCoV patients during the hospitalization and shortly after cure.
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High ACE2 expression has been found in several specific cell types across organs, including type II alveolar cells of lung, upper and stratified esophageal epithelial cells, absorptive enterocytes of ileum and colon, cholangiocytes, myocardial cells, kidney proximal tubule cells, and bladder urothelial cells.
“High ACE2 expression was identified in type II alveolar cells (AT2) of lung10–12, esophagus upper and stratified epithelial cells, absorptive enterocytes from ileum and colon12, cholangiocytes13, myocardial cells, kidney proximal tubule cells, and bladder urothelial cells10.”
From High expression of ACE2 receptor of 2019-nCoV on the epithelial cells of oral mucosa (2020) · cites this paper as [13]
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- Authors
- Chai, X., Hu, L., Zhang, Y., Han, W., Lu, Z., Ke, A., Zhou, J., Shi, G., Fang, N., Fan, J., Cai, J., Fan, J., & Lan, F.
- Affiliations
- Fudan University (CN)
- Singleron Biotechnologies (china) (CN)
- Corresponding author
- Cai, Jiabin
- Fan, Jue
- Lan, Fei
- Venue
- bioRxiv (Cold Spring Harbor Laboratory)
- Publisher
- openRxiv
- Published
- 2020-02-04
- OpenAlex
- W3004662718
- Cited by
- 952
- References
- 16
- Citations by year
- 2026: 7 · 2025: 15 · 2024: 42 · 2023: 80 · 2022: 147 · 2021: 275 · 2020: 382 · 2019: 3 · 2012: 1
- Type
- posted content
- Language
- en
- Open access
- green
- doi.org
- Licence
- Locations
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- Topics
- Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Keywords
- ACE2, cholangiocytes, SARS-CoV-2, liver injury, hepatocyte injury, viral receptor expression, liver injury mechanisms, systemic inflammatory response, drug-induced liver injury
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