Exosomes mediate protective messages during oxidative stress; role of exosomal shuttle RNA

Exosomes are small extracellular nano-vesicles of endocytic origin that mediate different signals between cells, by surface interactions and by shuttling of functional RNA from one cell to another. In this study, we show that exosomes, produced by mouse mast cells exposed to oxidative stress, change their mRNA content and also that these exosomes can influence the response of other cells to oxidative stress by providing recipient cells with a resistance against oxidative stress. Finally, we also show that UV-light affect the biological functions associated with exosomes released under oxidative stress. These results argue that exosomal shuttle of RNA is involved in cell-to-cell communication, by influencing the response of recipient cells to an external stimulus. We used microarrays to detail to examine the gene expression underlying the effect of H2O2 on the exosomal RNA and how exosomes isolated from oxidative stress influence the growth of recipient cells during oxidative stress. The mRNA content of the exosomes from normal conditions (MC9 Exo_norm) were compared to that from exosomes from H2O2 conditions (MC9 Exo_H2O2). The mRNA content of recipient cells MC9 were identified before (MC9 cells_norm) and after (MC9 cells_H2O2) addition of exosomes that were isolated from normal and H2O2 conditions.

外泌体（Exosomes）是一类源自内吞途径的小型细胞外纳米囊泡，可通过表面相互作用以及功能性RNA的跨细胞穿梭，介导细胞间的多种信号传递。本研究证实，经氧化应激处理的小鼠肥大细胞所分泌的外泌体，其mRNA组成会发生改变；且此类外泌体可通过赋予受体细胞氧化应激抗性，调控其他细胞对氧化应激的应答反应。此外，本研究还发现紫外线照射会影响氧化应激状态下释放的外泌体的生物学功能。上述结果表明，RNA的外泌体穿梭机制通过调控受体细胞对外部刺激的应答，参与了细胞间的信号交流。本研究利用基因芯片（microarrays），详细分析了过氧化氢（H₂O₂）对外泌体RNA的调控效应，以及氧化应激来源的外泌体如何影响受体细胞在氧化应激状态下的增殖情况。我们将正常培养条件下小鼠肥大细胞MC9分泌的外泌体（MC9 Exo_norm）的mRNA组成，与经H₂O₂处理组的外泌体（MC9 Exo_H2O2）进行了对比分析。我们还分别鉴定了添加外泌体前的MC9受体细胞（MC9 cells_norm），以及添加正常培养或H₂O₂处理来源外泌体后的MC9受体细胞（MC9 cells_H2O2）的mRNA组成。