Exosomes in the pathogenesis, diagnostics and therapeutics of liver diseases

Abstract

Summary Exosomes are small (30–100 nm in diameter) extracellular membrane-enclosed vesicles released by different cell types into the extracellular space or into biological fluids by exocytosis as a result of fusion of intracellular multivesicular bodies with the plasma membrane. The primary function of exosomes is intercellular communication with both beneficial (physiological) and harmful (pathological) potential outcomes. Liver cells are exosome-releasing cells as well as targets for endogenous exosomes and exosomes derived from cells of other organs. Despite limited studies on liver exosomes, initial observations suggest that these vesicles are important in liver physiology and pathophysiology. In this review, we briefly summarize the recent findings on liver exosomes, their functions and significance for novel diagnostic and therapeutic approaches.

Exosome Adherence and Internalization by Hepatic Stellate Cells Triggers Sphingosine 1-Phosphate-dependent Migration

“…In prior studies, the mechanism of exosome uptake has varied, and data exists to support each of these pathways (10,12,14,(57)(58)(59)(60). In this study, exosome endocytosis was mediated by dynamin because knockdown or inhibition of this protein attenuated exosome uptake and associated signaling.…”

Hepatic sinusoids in liver injury, inflammation, and fibrosis: new pathophysiological insights

“…However, in recent years exosomes have been increasingly recognized as a new way of intercellular communication by promoting protein and lipid exchange between exosome producing cells and target cells [67]. Exosomes are extracellular membrane-enclosed vesicles, produced in multivesicular bodies (MVB) and released into the extracellular space or into biological fluids by fusion of MVB with the plasma membrane [68]. They are characterized by the following criteria: diameter of 40-100 nm, density of 1.13-1.19 g/mL, cup-or deflated footballshaped morphology, and a sediment at 100,000 9g [67].…”

“…Different cells in different organs and tissues have been identified as exosome producing or target cells [73]. In the liver, those are liver epithelia (hepatocytes, cholangiocytes), natural killer T cells, HSC, and SEC [68]. Of interest, liver cells have been shown to be targets even for exosomes originating from other organs such as the intestine [74].…”

“…Of interest, liver cells have been shown to be targets even for exosomes originating from other organs such as the intestine [74]. The current knowledge about the role of exosomes in liver diseases has been discussed previously by Masyuk et al [68], who reviewed the involvement of exosomes in HCC, HCV, and liver inflammation, and their potential role as early diagnostic and prognostic markers from the urine or blood. Herein, we highlight the role of exosome signaling in HSC-SEC crosstalk.…”

Reply to: “Doublecortin domain containing protein 2 (DCDC2) genetic variants in primary sclerosing cholangitis”

“…Letter to the editor Although no disease causing variants in cilia related genes have been so far identified in patients with PSC the altered expression and mislocalisation of cilial proteins could still be implicated in the disease pathogenesis of PSC [3][4][5]. It has been suggested though that this effect is more likely part of a secondary sequalae of changes in the biliary microenvironment rather than the primary cause [6].…”