Abstract
Recent findings have revealed that extracellular vesicles (EVs) are secreted from cells and circulate in the blood. EVs are classified as exosomes (40−100 nm), microvesicles (50−1,000 nm) or apoptotic bodies (500−2,000 nm). EVs contain mRNAs, microRNAs, and DNAs and have the ability to transfer them from cell to cell. Recently, especially in humans, the diagnostic accuracy of tumor cell type-specific EV-associated miRNAs as biomarkers has been found to be more than 90 %. In addition, microRNAs contained in EVs in blood are being identified as specific biomarkers of chemical-induced inflammation and organ damage.Therefore, microRNAs contained in the EVs released into the blood from tissues and organs in response to adverse events such as exposure to chemical substances and drugs are expected to be useful as novel biomarkers for toxicity assessment. In this study, C57BL/6 J male mice orally dosed with carbon tetrachloride (CCl4) were used as a hepatotoxicity animal model. Here, we report that not only the known hepatotoxicity biomarkers miR-122 and miR-192 but also 42 novel EV-associated biomarkers were upregulated in mice dosed with CCl4. Some of these novel biomarkers may be expected to be able to use for better understanding the mechanism of toxicity. These results suggest that our newly developed protocol using EV-associated miRNAs as a biomarker would accelerate the rapid evaluation of toxicity caused by chemical substances and/or drugs.
Highlights
Exosomes are a subset of extracellular vesicles (EVs), which are lipid bilayer vesicles secreted from cells that have a diameter of 40–100 nm [1]
The peak size of the EV RNA was approximately 20–150 nt, and there was no obvious peak for the 18S & 28S ribosomal subunits, suggesting that these RNAs were derived from EVs rather than cellular RNAs
AST and ALT are known to be very good biomarkers of liver damage; it is difficult to distinguish the cause of liver damage or status of the liver based on only elevated levels of AST and ALT
Summary
Exosomes are a subset of extracellular vesicles (EVs), which are lipid bilayer vesicles secreted from cells that have a diameter of 40–100 nm [1]. Exosomes are endosomal in origin and contain proteins, lipids, DNA, mRNA, noncoding RNA, and small RNAs and are important mediators of cell-cell communication and horizontal gene transfer [2] [3] [4]. Several types of EVs other than exosomes have been identified. They include microvesicles (50–1000 nm) and apoptotic bodies (500–2000 nm). We will use the term “EVs” as recommended by the International Society for Extracellular Vesicles, which includes vesicles present in the extracellular space (exosomes, microvesicles and apoptotic bodies) [8]
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