Exosomes Communicate Protective Messages during Oxidative Stress; Possible Role of Exosomal Shuttle RNA

TLDR

Exosomes are small extracellular vesicles released by many cell types that mediate intercellular signaling through surface interactions and RNA shuttling, and they differ from their donor cells in size and molecular composition. The study investigates whether exosomes released by mouse mast cells under oxidative stress have altered mRNA content. Exosomes were isolated from mouse mast cells exposed to oxidative stress and their mRNA profiles were compared to those from unstressed cells. Exosomes from stressed mast cells carry distinct mRNA profiles that confer resistance to oxidative stress in recipient cells, reduce viability loss, and exhibit altered biological functions when exposed to UV light, supporting a role for exosomal RNA in stress‑mediated intercellular communication.

Abstract

Background Exosomes are small extracellular nanovesicles of endocytic origin that mediate different signals between cells, by surface interactions and by shuttling functional RNA from one cell to another. Exosomes are released by many cells including mast cells, dendritic cells, macrophages, epithelial cells and tumour cells. Exosomes differ compared to their donor cells, not only in size, but also in their RNA, protein and lipid composition. Methodology/Principal Findings In this study, we show that exosomes, released by mouse mast cells exposed to oxidative stress, differ in their mRNA content. Also, we show that these exosomes can influence the response of other cells to oxidative stress by providing recipient cells with a resistance against oxidative stress, observed as an attenuated loss of cell viability. Furthermore, Affymetrix microarray analysis revealed that the exosomal mRNA content not only differs between exosomes and donor cells, but also between exosomes derived from cells grown under different conditions; oxidative stress and normal conditions. Finally, we also show that exposure to UV-light affects the biological functions associated with exosomes released under oxidative stress. Conclusions/Significance These results argue that the exosomal shuttle of RNA is involved in cell-to-cell communication, by influencing the response of recipient cells to an external stress stimulus.