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Case Reports in Surgery and Invasive Procedures | Volume 3
March 11-12, 2019 | London, UK
Biomarkers
Plastic and Cosmetic Surgery
International Conference on
International Conference on
Joint Event
&
Extracellular vesicles and their microRNA cargo serve as biomarkers and communicators in liquid bi-
opsies in liver disease
Gyongyi Szabo
University of Massachusetts Medical School, USA
L
iquid biopsies (serum or plasma) are of great interest in the
diagnosis and prognostication of liver diseases. Extracellular
vesicles (EVs), that contain nucleic acids including microRNAs
and proteins are produced by most cell types in the liver,
are being exploited in biomarker discovery. We have shown
that different types of liver injury (alcoholic, drug-induced or
inflammation-related) result in increased levels of circulating
EVs and these EVs are enriched in miR-122 indicating
hepatocyte injury or miR-155 indicating liver inflammation.
We found significantly increased number of circulating EVs in
mice with alcoholic liver disease (ALD). Exosomes represented
most of the EVs (~80%). MicroRNA array of EVs revealed a
significant increase of 7 inflammatory miRs (miR-192, -122,
-30a) in alcohol-fed mice compared to controls and of those
miRNAs showed excellent diagnostic value by ROC analyses. In
patients with acute alcoholic hepatitis, we found a significant
increase in the number of circulating EVs compared to controls
with an increase in miR-192 and miR-30a in their cargo. Mass
spectrometric analysis of circulating EVs in mice revealed
a distinct signature of proteins involved in inflammatory
responses, cellular development, and cellular movement
between ALD EVs and control EVs. We also identified uniquely
important proteins in ALD EVs that were not present in control
EVs. Finally, we found that ALD EVs injected intravenously
into alcohol naive mice were taken up by hepatocytes and
MØs in the recipients’ livers. The biological activity of ALD
EVs in recipient mice was indicated by increased numbers of
inflammatory (M1) Kupffer cells and infiltrating macrophages,
while the percentage of anti-inflammatory (M2) macrophages
was decreased. We identified heat shock protein 90 in ALD EVs
as the mediator of ALD-EV - induced macrophage activation.
These results indicate a specific miRNA and protein signature
of ALD EVs and demonstrate a functional role of circulating
EVs in ALD.
e:
Gyongyi.Szabo@umassmed.edu