Circulating exosomes from lipopolysaccharide-induced ards mice trigger endoplasmic reticulum stress in lung tissue

Background: Acute respiratory distress syndrome (ARDS) is a critical clinical syndrome with high mortality rate, and few effective therapies have been found in the past 50 years, indicating that the pathogenesis of ARDS remains unclear. Exosomes, a novel cross-communication mechanism, are involved in critical diseases. However, the role of circulating exosomes in the development of ARDS remains poorly understood. Methods: In the present study, naive mice were treated with circulating exosomes from lipopolysaccharide (LPS)-induced ARDS mice or exosome-depleted serum. Histological lung damage, bronchoalveolar lavage fluid (BALF), and endoplasmic reticulum (ER) stress were measured. Results: Increased tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, total cell counts, polymorphonuclear (PMN) leukocyte proportions and myeloperoxidase (MPO) activity in BALF, and increased wet/dry weight ratios and protein concentrations in BALF were found in mice after exosome injection but not in mice treated with exosome-depleted serum. Furthermore, western blot analysis showed that circulating exosomes from ARDS mice upregulated glucose-regulated protein 78 (GRP78) and C/EBP homologous protein (CHOP) expression and downregulated beta-Catenin and VE-cadherin expression in lung tissues. Conclusions: Collectively, these data demonstrate that circulating exosomes from LPS-induced ARDS mice trigger ER stress in lung tissue, facilitating the development of ARDS, at least partly by promoting endothelial dysfunction.