Bone marrow mesenchymal stem cell‐derived exosomes miR‐202‐5p inhibited pyroptosis to alleviate lung ischemic‐reperfusion injury by targeting CMPK2

Abstract Bone mesenchymal stem cell‐derived exosome (BMSC‐exosome) is a potential candidate for lung ischemia–reperfusion injury (LIRI) treatment. This study aims to investigate the anti‐pyroptosis effect of BMSC‐exosomes in LIRI. The LIRI cell model was established by hypoxia/reoxygenation (H/R) treatment. Interleukin (IL)‐1β and IL‐18 levels were examined by enzyme‐linked immunosorbent assay. Cell viability was assessed by 3‐(4,5‐dimethylthiazol‐2‐yl)‐2, 5‐diphenyltetrazolium bromide assay. Lactate dehydrogenase (LDH) release was examined using a LDH assay kit. The interaction between microRNA (miR)‐202‐5p and cytidine monophosphate kinase 2 (CMPK2) was analyzed using dual‐luciferase reporter assay and RNA immunoprecipitation. BMSC‐exosomes promoted cell viability and suppressed pyroptosis in H/R‐treated mouse lung epithelial. miR‐202‐5p was enriched in BMSC‐exosomes, and exosomal miR‐202‐5p inhibition upregulated pyroptosis‐associated proteins, including cleaved N‐terminal Gasdermin D, nucleotide‐binding domain‐like receptor family member pyrin domain‐containing protein 3, and Caspase1. Meanwhile, miR‐202‐5p suppressed CMPK2 expression by directly targeting CMPK2. Expectedly, CMPK2 knockdown reversed the promoting effect of exosomal miR‐202‐5p inhibition on pyroptosis in LIRI. Therefore, BMSC‐derived exosome miR‐202‐5p repressed pyroptosis to inhibit LIRI progression by targeting CMPK2.