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

BO Haimei; CAO Xinying; XING Pingchuan; WANG Zhijun

doi:10.12122/j.issn.1673-4254.2025.08.05

Abstract：Objective 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.Conclusion 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.