Abstract

Exosomes as Circulating Biomarkers for Liver Disease

Gyongyi Szabo, Professor, University of Massachusetts Medical School

Exosomes are heterogeneous membranous vesicles originating from multivesicular bodies in most cell types in the body. Recently, they emerged as potential biomarkers or disease, effective conveyors of intercellular communication, and vehicles for delivery of nucleic acid based therapy. Moreover, both the biomarker potential and pathophysiological roles for exosomes are beginning to be recognized in various liver diseases including alcoholic liver disease, hepatocellular carcinoma, non-alcoholic fatty liver disease, hepatitis B  and hepatitis C viral infections. The cargo of exosomes  may include nucleic acids, proteins and lipids. MicroRNAs and other non-coding RNAs received specific attention in biomarker discovery in liver diseases. Increasing evidence suggests that the composition of the cargo of exosomes is not a simple “sampling” of the cargo of the parental cell of the exosome. In fact, exosomes may contain miRNAs or other nucleic acids at higher or lower levels than their cells of origin. Furthermore, not only the number of released exosomes but also the content of exosomes can be different between diseased and normal states. For example, miRNA-122, that is most abundant in hepatocytes, was found to be increased in the circulation in various types of liver diseases including drug-induced liver injury, viral hepatitis, alcoholic and non-alcoholic liver disease in humans or animal models. The increased circulating miR-122 was in exosomes or in the plasma protein-rich fraction. miR-122 was also found in circulating exosomes  and recent studies suggest that hepatocyte-derived exosomes that contain miR-122  may have biological functions that are beyond their potential as biomarkers. For example, it was shown that alcohol-induced hepatocyte-derived exosomes contain  miR-122 and these exosomes can transfer miR-122 into immune cells (monocytes) resulting in a pro-inflammatory phenotypic change of monocytes. In this talk, the recent strides in