Abstract
Liver diseases are perpetuated by the orchestration of hepatocytes and other hepatic non-parenchymal cells. These cells communicate and regulate with each other by secreting mediators such as peptides, hormones, and cytokines. Extracellular vesicles (EVs), small particles secreted from cells, contain proteins, DNAs, and RNAs as cargos. EVs have attracted recent research interests since they can communicate information from donor cells to recipient cells thereby regulating physiological events via delivering of specific cargo mediators. Previous studies have demonstrated that liver cells secrete elevated numbers of EVs during diseased conditions, and those EVs are internalized into other liver cells inducing disease-related reactions such as inflammation, angiogenesis, and fibrogenesis. Reactions in recipient cells are caused by proteins and RNAs carried in disease-derived EVs. This review summarizes cell-to-cell communication especially via EVs in the pathogenesis of liver diseases and their potential as a novel therapeutic target.
Highlights
In non-alcoholic fatty liver disease (NAFLD) and its severe form non-alcoholic steatohepatitis (NASH), there is an interplay between hepatocytes, macrophages, and hepatic stellate cells (HSCs) detailed mechanisms of the orchestration of these cells are not well defined [3,4]
The authors have found that cholangiocytes at diseased conditions secrete Extracellular vesicles (EVs) containing H19, and cholangiocyte-derived EVs are internalized into hepatocytes suppressing small heterodimer partner by H19, which leads to increased bile acid synthesis resulting in cholestatic liver injury [72]
The majority of studies are based on hepatocytes as donor cells with EV secretion and macrophages as recipient cells with EV internalization
Summary
The liver consists of various types of cells with the majority of hepatocytes (~70% of liver cell population) that form the parenchyma of the liver [1]. In another study, stimulated hepatocyte-derived carcinoma cell line Huh cells and primary mouse hepatocytes with LPC secrete elevated numbers of EVs compared to those cells with vehicle, and LPC-derived EVs contain elevated levels of CXCL10 [30] These lipotoxic EVs induced cell migration and activation of bone marrow-derived macrophages in a CXCL10-dependent manner [30]. Exposure of hepatocytes to acetaminophen or galactatosamine increased EV secretion from hepatocytes in vitro, and administration of these drugs into mice caused liver damage and elevated numbers of circulating EVs in serum in vivo [32,33] These drug-derived EVs contained elevated amounts of proteins and different protein profiles. Since hepatocyte-derived EVs that contain elevated levels of miR-122 increase responses of THP-1 monocytes against lipopolysaccharide (LPS) [35], these studies suggest that hepatocytes release EVs that contain altered proteins and miRNAs to regulate the activation of monocytes and/or macrophages
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
