Insight into molecular mechanisms underlying hepatic dysfunction in severe COVID-19 patients using systems biology.
COVID-19
Drug metabolism
Hepatic detoxification
Hepatic dysfunction
Metabolic pathways
Tissue remodeling
Journal
World journal of gastroenterology
ISSN: 2219-2840
Titre abrégé: World J Gastroenterol
Pays: United States
ID NLM: 100883448
Informations de publication
Date de publication:
07 Jun 2021
07 Jun 2021
Historique:
received:
06
02
2021
revised:
30
03
2021
accepted:
10
05
2021
entrez:
17
6
2021
pubmed:
18
6
2021
medline:
22
6
2021
Statut:
ppublish
Résumé
The coronavirus disease 2019 (COVID-19), a pandemic contributing to more than 105 million cases and more than 2.3 million deaths worldwide, was described to be frequently accompanied by extrapulmonary manifestations, including liver dysfunction. Liver dysfunction and elevated liver enzymes were observed in about 53% of COVID-19 patients. To gain insight into transcriptional abnormalities in liver tissue of severe COVID-19 patients that may result in liver dysfunction. The transcriptome of liver autopsy samples from severe COVID-19 patients against those of non-COVID donors was analyzed. Differentially expressed genes were identified from normalized RNA-seq data and analyzed for the enrichment of functional clusters and pathways. The differentially expressed genes were then compared against the genetic signatures of liver diseases including cirrhosis, fibrosis, non-alcoholic fatty liver disease (NAFLD), and hepatitis A/B/C. Gene expression of some differentially expressed genes was assessed in the blood samples of severe COVID-19 patients with liver dysfunction using qRT-PCR. Analysis of the differential transcriptome of the liver tissue of severe COVID-19 patients revealed a significant upregulation of transcripts implicated in tissue remodeling including G-coupled protein receptors family genes, Severe COVID-19 patients appear to experience significant transcriptional shift that may ensue tissue remodeling, mitochondrial dysfunction and lower hepatic detoxification resulting in the clinically observed liver dysfunction.
Sections du résumé
BACKGROUND
BACKGROUND
The coronavirus disease 2019 (COVID-19), a pandemic contributing to more than 105 million cases and more than 2.3 million deaths worldwide, was described to be frequently accompanied by extrapulmonary manifestations, including liver dysfunction. Liver dysfunction and elevated liver enzymes were observed in about 53% of COVID-19 patients.
AIM
OBJECTIVE
To gain insight into transcriptional abnormalities in liver tissue of severe COVID-19 patients that may result in liver dysfunction.
METHODS
METHODS
The transcriptome of liver autopsy samples from severe COVID-19 patients against those of non-COVID donors was analyzed. Differentially expressed genes were identified from normalized RNA-seq data and analyzed for the enrichment of functional clusters and pathways. The differentially expressed genes were then compared against the genetic signatures of liver diseases including cirrhosis, fibrosis, non-alcoholic fatty liver disease (NAFLD), and hepatitis A/B/C. Gene expression of some differentially expressed genes was assessed in the blood samples of severe COVID-19 patients with liver dysfunction using qRT-PCR.
RESULTS
RESULTS
Analysis of the differential transcriptome of the liver tissue of severe COVID-19 patients revealed a significant upregulation of transcripts implicated in tissue remodeling including G-coupled protein receptors family genes,
CONCLUSION
CONCLUSIONS
Severe COVID-19 patients appear to experience significant transcriptional shift that may ensue tissue remodeling, mitochondrial dysfunction and lower hepatic detoxification resulting in the clinically observed liver dysfunction.
Identifiants
pubmed: 34135558
doi: 10.3748/wjg.v27.i21.2850
pmc: PMC8173390
doi:
Substances chimiques
DNAJB1 protein, human
0
HSP40 Heat-Shock Proteins
0
Steroid Hydroxylases
EC 1.14.-
CYP39A1 protein, human
EC 1.14.14.26
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
2850-2870Informations de copyright
©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
Déclaration de conflit d'intérêts
Conflict-of-interest statement: The authors declare no conflict of interest.
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