HMSCs exosome-derived miR-199a-5p attenuates sulfur mustard-associated oxidative stress via the CAV1/NRF2 signaling pathway

Abstract Background: Sulfur mustard (SM) is a blister-producing chemical warfare agent which could lead to a cascade of systemic damage, especially severe acute lung injury. Oxidative stress is considered to be vital processes for the SM toxicity mechanism. We previously proved the therapeutic effect of exosomes derived from bone marrow mesenchymal stromal cells in promoting the repair of alveolar epithelial barrier and inhibiting apoptosis. However, the key functional components in exosomes and the underlying mechanisms have not been fully elaborated. This research shed light on the function of the key components of human umbilical cord mesenchymal stem cell-derived exosomes. Results: We noted that HMSCs-Ex showed better antioxidant abilities to attenuate SM-induced apoptosis. Furthermore, it was identified that HMSCs-Ex-derived miR-199a-5p played the vital role in reducing pneumonocyte oxidative stress. We observed that the overexpression of miR-199a-5p in HMSCs-Ex exerted protective effects against SM-induced oxidative injury by activating the NRF2 signaling pathway. Moreover, it was confirmed that Caveolin1 (CAV1) was the target gene regulated by miR-199a-5p. MiR-199a-HMSCs-Ex reduced CAV1 expression, leading to the upregulation of NRF2 and the activation of the NRF2 antioxidant signal pathway. Conclusions: MiR-199a-5p was one of the key molecules in HMSCs-Ex that attenuated SM-associated oxidative stress via regulating CAV1/NRF2 signaling pathway.