Acinar Cells Derived Exosomes Alleviate the Severity of Acute Pancreatitis.

Acute pancreatitis (AP) is a serious and can be lethal disease, with an incidence of 13 to 45 per 100,000 individuals per year. The underlying mechanism of AP is not fully understood. Exosomes have recently been identified as intercellular messengers that can participate in the pathogenesis of various diseases. Exosomes secreted by noninflammatory acinar cells may affect the activated and injured acinar cells during AP.To investigate the effect of exosomes derived from acinar cells on the pathogenesis of AP.Nanoparticle tracking analysis was applied to evaluating the exosomes derived from AR42J acinar cells. The viability and apoptosis of AP in vitro model cells were evaluated. Wistar rats were used to establish the in vivo AP rat model and the levels of serum pro-inflammatory cytokines and morphological changes in the pancreatic tissues were assessed. RNA sequencing and Kyoto Encyclopedia of Genes and Genomes databases (KEGG) based RNA enrichment analyses were applied to exploring the mechanisms underlying the effect of exosomes on the pathogenesis of AP.Acinar cell exosomes reduced the level of intracellular ROS production and improved the viability of AP model acinar cells by inhibiting apoptosis during AP. The exosomes decreased the circulating levels of IL-6 and TNF-alpha, and reduced the pathological scores and wet/dry weight ratios of pancreatic tissue in AP in vivo model rats. Among the upregulated and downregulated RNAs analyzed, the MAPK and NF-kappaB signaling pathways might be involved in the mechanisms underlying the protective effects of acinar cell-derived exosomes in AP.Acinar cell-derived exosomes could reduce the apoptosis and ROS production in acinar cells during AP, and may alleviate the severity of AP via the MAPK and NF-kappaB signaling pathways.