Bile extracellular vesicles from end-stage liver disease patients show altered microRNA content View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2021-06-02

AUTHORS

Suguru Nakashiki, Satoshi Miuma, Hiroyuki Mishima, Hiroshi Masumoto, Masaaki Hidaka, Akihiko Soyama, Yasuko Kanda, Masanori Fukushima, Masafumi Haraguchi, Ryu Sasaki, Hisamitsu Miyaaki, Tatsuki Ichikawa, Mitsuhisa Takatsuki, Susumu Eguchi, Koh-ichiro Yoshiura, Kazuhiko Nakao

ABSTRACT

BackgroundExtracellular 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.MethodsBile 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.ResultsNanoparticle 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.ConclusionsSecretion 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. More... »

PAGES

821-830

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s12072-021-10196-5

DOI

http://dx.doi.org/10.1007/s12072-021-10196-5

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1138525347

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/34076850


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18 schema:description BackgroundExtracellular 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.MethodsBile 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.ResultsNanoparticle 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.ConclusionsSecretion 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.
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25 schema:keywords EV concentration
26 MethodsBile samples
27 PCR validation
28 alcoholic end-stage liver disease
29 analysis
30 attention
31 bile
32 biomarkers
33 carcinoma
34 concentration
35 content
36 content increases
37 diagnostic biomarkers
38 differences
39 disease
40 disease patients
41 diversity
42 donors
43 eV
44 end-stage liver disease
45 end-stage liver disease patients
46 expression
47 extracellular vesicles
48 failure
49 group
50 hepatocellular carcinoma
51 high-expression miRNAs
52 identification
53 increase
54 levels
55 liver
56 liver disease
57 liver disease patients
58 liver failure
59 liver state
60 liver transplant recipients
61 miR-17
62 miR-25
63 miR-423
64 miR-451a
65 miR-92a
66 miRNA levels
67 miRNAs
68 microRNAs
69 next-generation sequencing
70 novel biomarkers
71 novel diagnostic biomarkers
72 patients
73 potential biomarkers
74 quantitative PCR validation
75 recipients
76 report
77 samples
78 sequencing
79 serum EVs
80 significant differences
81 state
82 therapeutic tool
83 tool
84 tracking analysis
85 transplant recipients
86 transplantation
87 types
88 types of microRNAs
89 ultracentrifugation
90 validation
91 vesicles
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