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Duchenne muscular dystrophy(DMD)is a progressive disease characterized by skeletal muscle atrophy,respiratory failure,and cardiomyopathy.Our previous studies have shown that transplantation with allogeneic myogenic progenitor-derived exosomes(MPC-Exo)can improve cardiac function in X-linked muscular dystrophy(Mdx)mice.In the present study we explored the molecular mechanisms underlying this beneficial effect.We quantified gene expression in the hearts of two strains of Mdx mice(D2.B10-DmdMdx/J and Utrntm1Ked-DmdMdx/J).Two days after MPC-Exo or control treatment,we performed unbiased next-generation RNA-sequencing to identify differentially expressed genes(DEGs)in treated Mdx hearts.Venn diagrams show a set of 780 genes that were≥2-fold upregulated,and a set of 878 genes that were≥2-fold downregulated,in both Mdx strains following MPC-Exo treatment as compared with control.Gene ontology(GO)and protein-protein interaction(PPI)network analysis showed that these DEGs were involved in a variety of physiological processes and pathways with a complex connection.qRT-PCR was performed to verify the upregulated ATP2B4 and Bcl-2 expression,and downregulated IL-6,MAPK8 and Wnt5a expression in MPC-Exo-treated Mdx hearts.Western blot analysis verified the increased level of Bcl-2 and decreased level of IL-6 protein in MPC-Exo-treated Mdx hearts compared with control treatment,suggesting that anti-apoptotic and anti-inflammatory effects might be responsible for heart function improvement by MPC-Exo.Based on these findings,we believed that these DEGs might be therapeutic targets that can be explored to develop new strategies for treating DMD.