[Exosome-derived miR-1275 mediates IL-38 upregulation in lymphocytes to suppress lipopolysaccharide-induced apoptosis of myocardial cells ].

OBJECTIVES

To investigate the effect of cardiomyocytes-derived exosomes on lipopolysaccharide (LPS)-induced cardiomyocyte injury and its mechanism.

METHODS

Exosomes isolated from rat cardiomyocytes with or without LPS treatment were co-cultured with rat lymphocytes. The lymphocytes with or without exosome treatment were co-cultured with LPS-induced rat cardiomyocytes for 48 h. Cardiomyocyte apoptosis was detected using flow cytometry, and the expressions of apoptosis marker proteins and the PI3K/AKT pathway proteins were detected using Western blotting. The effects of human recombinant IL-38 protein on apoptosis and protein expressions in LPS-induced cardiomyocytes were examined.

RESULTS

Compared with normal cardiomyocyte-derived exosomes, the exosomes from LPS-induced cardiomyocytes significantly enhanced proliferation and increased mRNA and protein expression levels of IL-38 in rat lymphocytes. Bioinformatics analysis suggested that miR-1275 in the exosome played a key role in LPS-induced cardiomyocyte injury, and in dual luciferase reporter gene assay, miR-1275 mimics significantly increased luciferase activity of WT-IL-38. Co-culture with lymphocytes treated with exosomes from LPS-induced cardiomyocytes significantly inhibited apoptosis of LPS-induced cardiomyocytes. Treatment with recombinant IL-38 also effectively lowered apoptosis rate of LPS-induced cardiomyocytes, reduced cellular expression of Bax protein, and increased the protein expression levels of Bcl-2, p-PI3K and p-AKT.

CONCLUSIONS

miR-1275 in exosomes derived from LPS-induced cardiomyocytes mediates IL-38 up-regulation expression in lymphocytes to activate the PI3K/AKT pathway and inhibit LPS-induced cardiomyocyte apoptosis.