38. Evaluation of exosomal microRNA expression following exposure to acute stress

Abstract

Exosomes, biologically active nanoparticles released by most cells in the body, express a variety of proteins and contain small, non-coding RNA known as microRNA (miRNA). Exosomal miRNA are transferred to recipient cells where they regulate target genes and modulate translation of messenger RNA. We have previously reported that exposure to an acute, intense stressor (tailshock) modifies plasma exosome-associated heat shock protein expression. It remains unknown, however, if stressor exposure also modulates miRNA exosome expression. We hypothesize that exposure to an acute stressor induces miRNA modifications in plasma exosomes and that these modifications are a critical component of the stress response. Male Fisher 344 rats (3/group) were subjected to tail shock stress or no stress, and exosome isolation from plasma was verified by size (Nanosight) and common exosome markers (CD63, Rab5b, A33). Stress response was verified by spleen weight, blood glucose, and exosome expression of heat shock protein 72. We report that exposure to an acute stressor significantly down-regulates exosome expression of miR-142-5p (−17%), miR-203-3p (−8%), and miR-155 (−8%) in plasma exosomes compared to no stress controls. Suppression of these miRNA could decrease TLR expression, IgG expression, and apoptosis. Additionally, reduction of miR-142 could promote activation of CD4+ T cells. These findings suggest that exposure to stress modifies miRNA on circulating exosomes, potentially impacting apoptosis and immunity during stress. Supported by NSF IOS 1022451.