Prophylactic treatment with MSC derived exosomes attenuates traumatic acute lung injury. - GreenMedInfo Summary

Mesenchymal stem cell (MSC) is a potential strategy in the pretreatment of traumatic acute lung injury (ALI), a disease which causes inflammation and oxidative stress (OS). This study aimed to investigate whether MSCs-exosomal microRNA-124-3p (miR-124-3p) affects traumatic ALI. Initially, a traumatic ALI rat model was established using the weight-drop method. Then, exosomes were obtained from MSCs of Sprague-Dawley (SD) rats, which were injected into the traumatic ALI rats. We found that miR-124-3p was abundantly-expressed in MSCs-derived exosomes and could directly target purinergic receptor P2X ligand-gated ion channel 7 (P2X7), which was over-expressed in traumatic ALI rats. After that, a loss- and gain-of-function study was performed in MSCs and traumatic ALI rats to investigate the role of miR-124-3p and P2X7 in traumatic ALI. MSC-derived exosomal miR-124-3p or silenced P2X7 were observed to increase the survival rate of traumatic ALI rats and enhance the glutathione (GSH)/ superoxide dismutase (SOD) activity in their lung tissues. However, the wet/dry weight of lung tissues, activity of methylenedioxyamphetamine (MDA) and HO, and levels of inflammatory factors (TNF-a, IL-6, and IL-8) were reduced. Similarly, the numbers of total cells, macrophages, neutrophils and lymphocytes in bronchoalveolar lavage fluid (BALF) were also reduced when treated with exosomal miR-124-3p or silenced P2X7. In conclusion, the results provide evidence that miR-124-3p transferred by MSCs-derived exosomes inhibited P2X7 expression, thus improving OS injury and suppressing inflammatory response in traumatic ALI, highlighting a potential pretreatment for traumatic ALI.