Bile extracellular vesicles from end-stage liver disease patients show altered microRNA content.
Alcoholic liver disease
Biomarker
Exosome
Hepatocellular carcinoma
Liver failure
Liver transplantation
MiRNA-17
Nanoparticle tracking analysis
Next-generation sequencing
Ultracentrifugation
Journal
Hepatology international
ISSN: 1936-0541
Titre abrégé: Hepatol Int
Pays: United States
ID NLM: 101304009
Informations de publication
Date de publication:
Jun 2021
Jun 2021
Historique:
received:
28
01
2021
accepted:
17
04
2021
pubmed:
3
6
2021
medline:
30
10
2021
entrez:
2
6
2021
Statut:
ppublish
Résumé
Extracellular vesicles (EVs) have recently attracted attention as novel diagnostic biomarkers and therapeutic tools. Several reports have correlated blood EVs with liver diseases. However, blood EVs do not reflect the liver state as it contains other systemically circulating EVs. Therefore, we focused on bile EVs, which are secreted directly from the liver, for the identification of potential biomarkers of liver failure. Bile samples were collected from liver transplant recipients (n = 21) diagnosed with end-stage liver disease (ESLD) and donors (normal liver, NL; n = 18) during transplantation. Bile EVs were extracted using ultracentrifugation. Nanoparticle tracking analysis showed that bile EV concentration was significantly higher in recipients than in donors. Among recipients, bile EV concentration was remarkably higher in those with hepatocellular carcinoma. Next-generation sequencing revealed 461 and 465 types of microRNAs (miRNAs) in donor and recipient bile EVs, respectively, with no significant difference in diversity between the groups. Among 43 high-expression miRNAs, the expression of 86.0% of the miRNAs was higher in the bile EVs of recipients than in those of donors. Quantitative PCR validation showed that the levels of miR-17, miR-92a, miR-25, miR-423, and miR-451a significantly increased in bile EVs of recipients. Levels of miR-17 were remarkably higher in recipients with alcoholic ESLD. Secretion of EVs into the bile and their miRNA content increase in the ESLD state. Additionally, miRNA levels in bile EVs are not correlated with those in serum EVs. Bile EVs could be promising novel biomarkers for liver diseases.
Sections du résumé
BACKGROUND
BACKGROUND
Extracellular vesicles (EVs) have recently attracted attention as novel diagnostic biomarkers and therapeutic tools. Several reports have correlated blood EVs with liver diseases. However, blood EVs do not reflect the liver state as it contains other systemically circulating EVs. Therefore, we focused on bile EVs, which are secreted directly from the liver, for the identification of potential biomarkers of liver failure.
METHODS
METHODS
Bile samples were collected from liver transplant recipients (n = 21) diagnosed with end-stage liver disease (ESLD) and donors (normal liver, NL; n = 18) during transplantation. Bile EVs were extracted using ultracentrifugation.
RESULTS
RESULTS
Nanoparticle tracking analysis showed that bile EV concentration was significantly higher in recipients than in donors. Among recipients, bile EV concentration was remarkably higher in those with hepatocellular carcinoma. Next-generation sequencing revealed 461 and 465 types of microRNAs (miRNAs) in donor and recipient bile EVs, respectively, with no significant difference in diversity between the groups. Among 43 high-expression miRNAs, the expression of 86.0% of the miRNAs was higher in the bile EVs of recipients than in those of donors. Quantitative PCR validation showed that the levels of miR-17, miR-92a, miR-25, miR-423, and miR-451a significantly increased in bile EVs of recipients. Levels of miR-17 were remarkably higher in recipients with alcoholic ESLD.
CONCLUSIONS
CONCLUSIONS
Secretion of EVs into the bile and their miRNA content increase in the ESLD state. Additionally, miRNA levels in bile EVs are not correlated with those in serum EVs. Bile EVs could be promising novel biomarkers for liver diseases.
Identifiants
pubmed: 34076850
doi: 10.1007/s12072-021-10196-5
pii: 10.1007/s12072-021-10196-5
doi:
Substances chimiques
Biomarkers
0
MicroRNAs
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
821-830Informations de copyright
© 2021. Asian Pacific Association for the Study of the Liver.
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