MSC-derived (EVs) showed protective effects against hyperoxia-induced lung injuries in a animal model.
-203a-3p (miR-203a-3p) in MSC-derived EVs inhibited cell death caused by high oxygen levels.
miR-203a-3p reduced inflammation by targeting specific proteins involved in the inflammatory response.
Experiments indicated that the presence of miR-203a-3p enhanced the therapeutic effects of MSC-derived EVs compared to control EVs.
The study suggests that miR-203a-3p is a significant factor contributing to the protective effects of MSC-derived EVs in treating BPD.
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BACKGROUND: (BPD) is the most well-known disease contributing to mortality and long-term morbidity in premature infants. Although the pathogenesis of BPD is multifactorial, hyperoxia-induced lung injury and inflammation are recognized as major causes of BPD. (EV) are known to function as a powerful cell-cell communicator by delivering their cargo including proteins, lipids, and nucleic acids such as . EVs derived from mesenchymal stem cells (MSC) are recently reported as promising and effective therapeutic modalities for BPD.
METHODS: The therapeutic effects of MSC-derived EV were examined using a BPD animal model. Differentially expressed miRNAs were selected through miRNA sequencing. The regulation of target genes by miRNA was investigated by Western blot, RT-qPCR, Ago2 RNA immunoprecipitation, and luciferase reporter assay. The increase in therapeutic efficacy of EVs by miRNA was demonstrated by confirming the anti-apoptotic and anti-inflammatory effects of EVs secreted by HEK293 cells overexpressing miR-203a-3p.
RESULTS: Through an in vivo BPD animal model, MSC-derived EVs exhibited protective effects against hyperoxia-induced lung injuries. To define the molecular mechanisms by which MSC-derived EVs alleviate BPD, anti-apoptotic and anti-inflammatory effects were examined. MicroRNA-203a-3p (miR-203a-3p) present in MSC-derived EVs exhibited inhibitory effects on HO-induced apoptotic cell death by targeting inhibitor of differentiation 4, as well as on lipopolysaccharide-induced inflammatory cytokine expression by targeting myeloid differentiation primary response 88. Experiments with miR-203a-3p inhibitor revealed that miR-203a-3p was responsible for mitigative effects of MSC-derived EVs. Compared to EVs containing control mimic, EVs containing miR-203a-3p mimic exhibited higher anti-apoptotic and anti-inflammatory effects. 2 2
CONCLUSIONS: Our findings revealed that miR-203a-3p in MSC-derived EVs inhibited apoptotic cell death and inflammation, demonstrating that miR-203a-3p is a key player enabling MSC-derived EVs to exhibit therapeutic effects for BPD.
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