Biological Functions of Exosomes in the Liver in Health and Disease

Implication for health policy/practice/research/medical education: Exosomes contribute to both liver restoration and damaging; therefore, controlling their release may be useful in prevention and treatment of liver diseases. In addition, designing a novel tool based on exosome may be useful in gene therapy. The liver is a complicated environment comprised of several different cell types such as hepatocytes, paren-chymal cells, Kupffer cells, natural killer cells, B cells, T cells, and stellate cells (1, 2), which are involved in various functions necessary for maintaining of the health. To maintain the proper function of the liver, coordination between all cell types population is necessary. One of the potent mechanisms involved in this harmonic orchestra is the exosome, 30-100 nm extracellular nanovesicles with the endosomal origin. Exosome contains various proteins, lipids, and genetic materials including mRNAs and microRNAs (miRNAs), which is closely associated with the content of cell released from. After secretion, the exosome can attach to the target cell, fuse with the membrane , deplete the cargos and finally, it can exchange the biological information with recipient cells that leads to promoting or inhibiting diverse signals. Hosseini et al. have published a useful review to shed light on these subjects (3). In spite of few data concerning the role of secreted exosome by liver cells, it is approved that the type and content of exosomes are different in the physiological and pathological conditions. This discrepancy can conduct the fate and behavior of the cells (Figure 1) (4). For instance, in the oxidative stress, released exosome have a transcriptome to modulate stress conditions via altering a pattern of gene expression. This event leads to prime the recipient cells for combating the new condition. The presence of the drug and xenobiotic metabolizing enzymes such as cytochrome p450 family, uridine nucleotide diphosphate glucuronosyltransferase (UDPGT) and glutathione S-transferase within the hepatic exosomes and their release in human plasma has been confirmed (5). Therefore, these vesicles can assist tissues other than the liver to protect themselves against various toxicant. In addition, vesicle secretion from the cell may play a significant role in the emerging drug resistance. Hennessy et al. revealed that the presence of P-glycoprotein, which is involved in the multidrug resistance through the efflux of drug into the extracellular space, can be the cause of resistance in the sensitive cells after coculturing with the resistant cell lines (6). In addition to regenerating the injured tissues, exo-some are …