Abstract
Exosomes are extracellular vesicles with diameters ranging from 30 to 150 nm, which contain several donor cell‐associated proteins as well as mRNA, miRNA, and lipids and coordinate multiple physiological and pathological functions through horizontal communication between cells. Almost all types of liver cells, such as hepatocytes and Kupffer cells, are exosome‐releasing and/or exosome‐targeted cells. Exosomes secreted by liver cells play an important role in regulating general physiological functions and also participate in the onset and development of liver diseases, including liver cancer, liver injury, liver fibrosis and viral hepatitis. Liver cell‐derived exosomes carry liver cell‐specific proteins and miRNAs, which can be used as diagnostic biomarkers and treatment targets of liver disease. This review discusses the functions of exosomes derived from different liver cells and provides novel insights based on the latest developments regarding the roles of exosomes in the diagnosis and treatment of liver diseases.
Highlights
Exosomes are primarily derived from multi-vesicular bodies, which fuse with the plasma membrane and subsequently release internal vesicles in the form of exosomes.[1]
Exosomes contain a variety of biologically active molecules, including lipids, proteins and nucleic acids, such as mRNA, microRNA and long non-coding RNA
Hepatocyte-derived exosomes were observed to promote the proliferation of hepatocytes in vitro and liver regeneration in vivo by mediating the transfer of sphingosine kinase 2 (SK2) to target cells and inducing up-regulation of intracellular sphingosine-1-phosphate (S1P).[30,31]
Summary
Exosomes are primarily derived from multi-vesicular bodies, which fuse with the plasma membrane and subsequently release internal vesicles in the form of exosomes.[1]. Hepatocytederived exosomes could transfer functional miRNAs and multiple immune-mediated transcripts to monocytes to inhibit the release of cytokine stimulated by LPS.[28,29] In addition, hepatocyte-derived exosomes were observed to promote the proliferation of hepatocytes in vitro and liver regeneration in vivo by mediating the transfer of sphingosine kinase 2 (SK2) to target cells and inducing up-regulation of intracellular sphingosine-1-phosphate (S1P).[30,31]. Researchers found that, in multidrug resistance-associated protein 2 knockout mice, exosomes secreted by cholangiocytes can transfer lncRNA-H19 to hepatocytes; this subsequently inhibits the expression of hepatic small heterodimer partner, interferes with bile acid homoeostasis and promotes cholestatic liver injury.[36] Research showed that exosomes containing lncRNA-H19 are major contributors to liver fibrosis.
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