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Circulating Extracellular Vesicles with Specific Proteome and Liver MicroRNAs Are Potential Biomarkers for Liver Injury in Experimental Fatty Liver Disease

Open access
Povero, Davide, Eguchi, Akiko, Li, Hongying, Johnson, Casey D., Papouchado, Bettina G., Wree, Alexander, Messer, Karen, Feldstein, Ariel E.·2014·PLoS ONE

Abstract

BACKGROUND & AIM: Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in both adult and children. Currently there are no reliable methods to determine disease severity, monitor disease progression, or efficacy of therapy, other than an invasive liver biopsy. DESIGN: Choline Deficient L-Amino Acid (CDAA) and high fat diets were used as physiologically relevant mouse models of NAFLD. Circulating extracellular vesicles were isolated, fully characterized by proteomics and molecular analyses and compared to control groups. Liver-related microRNAs were isolated from purified extracellular vesicles and liver specimens. RESULTS: We observed statistically significant differences in the level of extracellular vesicles (EVs) in liver and blood between two control groups and NAFLD animals. Time-course studies showed that EV levels increase early during disease development and reflect changes in liver histolopathology. EV levels correlated with hepatocyte cell death (r2 = 0.64, p<0.05), fibrosis (r2 = 0.66, p<0.05) and pathological angiogenesis (r2 = 0.71, p<0.05). Extensive characterization of blood EVs identified both microparticles (MPs) and exosomes (EXO) present in blood of NAFLD animals. Proteomic analysis of blood EVs detected various differentially expressed proteins in NAFLD versus control animals. Moreover, unsupervised hierarchical clustering identified a signature that allowed for discrimination between NAFLD and controls. Finally, the liver appears to be an important source of circulating EVs in NAFLD animals as evidenced by the enrichment in blood with miR-122 and 192--two microRNAs previously described in chronic liver diseases, coupled with a corresponding decrease in expression of these microRNAs in the liver. CONCLUSIONS: These findings suggest a potential for using specific circulating EVs as sensitive and specific biomarkers for the noninvasive diagnosis and monitoring of NAFLD.

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Metadata

Authors
Povero, D., Eguchi, A., Li, H., Johnson, C. D., Papouchado, B. G., Wree, A., Messer, K., & Feldstein, A. E.
Venue
PLoS ONE
Published
2014-12-03
Volume
9
Issue
12
Pages
e113651
ISSN
1932-6203 (ISSN-L)
OpenAlex
W2052478346
Cited by
272
References
52
FWCI
7.06
Type
journal article
Language
en
Open access
gold

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CoChat. (2026). Citation check: Circulating Extracellular Vesicles with Specific Proteome and Liver MicroRNAs Are Potential Biomarkers for Liver Injury in Experimental Fatty Liver Disease. https://app.cochat.ai/papers/10.1371/journal.pone.0113651
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Povero, D., Eguchi, A., Li, H., Johnson, C. D., Papouchado, B. G., Wree, A., Messer, K., & Feldstein, A. E. (2014). Circulating Extracellular Vesicles with Specific Proteome and Liver MicroRNAs Are Potential Biomarkers for Liver Injury in Experimental Fatty Liver Disease. PLoS ONE. https://doi.org/10.1371/journal.pone.0113651

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