title: Extracellular vesicles in liver pathobiology: Small particles with big impact.
abstract: Extracellular vesicles (EVs) are nanometer-sized, membrane-bound vesicles released by cells into the extracellular milieu. EVs are now recognized to play a critical role in cell-to-cell communication. EVs contain important cargo in the form of proteins, lipids, and nucleic acids and serve as vectors for delivering this cargo from donor to acceptor or target cell. EVs are released under both physiologic and pathologic conditions, including liver diseases, and exert a wide range of effects on target cells. This review provides an overview on EV biogenesis, secretion, cargo, and target cell interactions in the context of select liver diseases. Specifically, the diverse roles of EVs in nonalcoholic steatohepatitis, alcoholic liver disease, viral hepatitis, cholangiopathies, and hepatobiliary malignancies are emphasized. Liver diseases often result in an increased release of EVs and/or in different cargo sorting into these EVs. Either of these alterations can drive disease pathogenesis. Given this fact, EVs represent a potential target for therapeutic intervention in liver disorders. Because altered EV composition may reflect the underlying disease condition, circulating EVs can be exploited for diagnostic and prognostic purposes as a liquid biopsy. Furthermore, ex vivo modified or synthesized EVs can be engineered as therapeutic nano-shuttles. Finally, we highlight areas that merit further investigation relevant to understanding how EVs regulate liver disease pathogenesis. (Hepatology 2016;64:2219-2233).
authors.affiliation: Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN.
authors.forename: Petra
authors.initials: P
authors.lastname: Hirsova
authors.affiliation: Division of Pediatric Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN.
authors.forename: Samar H
authors.initials: SH
authors.lastname: Ibrahim
authors.affiliation: Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN.
authors.forename: Vikas K
authors.initials: VK
authors.lastname: Verma
authors.affiliation: Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN.
authors.forename: Leslie A
authors.initials: LA
authors.lastname: Morton
authors.affiliation: Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN.
authors.forename: Vijay H
authors.initials: VH
authors.lastname: Shah
authors.affiliation: Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN.
authors.forename: Nicholas F
authors.initials: NF
authors.lastname: LaRusso
authors.affiliation: Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN.
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Gores
authors.affiliation: Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN.
authors.forename: Harmeet
authors.initials: H
authors.lastname: Malhi
mesh_terms: D000818:Animals; D002450:Cell Communication; D000067128:Extracellular Vesicles / Q000502:physiology; D006505:Hepatitis / Q000209:etiology / Q000473:pathology; D006801:Humans; D008107:Liver Diseases / Q000209:etiology / Q000473:pathology*; D065626:Non-alcoholic Fatty Liver Disease / Q000209:etiology / Q000473:pathology; D001678:Organelle Biogenesis