Exosome-derived miR-1275 mediates IL-38 upregulation in lymphocytes to suppress lipopolysaccharide-induced apoptosis of myocardial cells in vitro.
10.12122/j.issn.1673-4254.2025.08.05
- Author:
Haimei BO
1
;
Xinying CAO
2
;
Pingchuan XING
1
;
Zhijun WANG
2
Author Information
1. School of Clinical Medicine, North China University of Science and Technology, Tangshan 063000, China.
2. Affiliated Hospital of North China University of Science and Technology, Tangshan 063000, China.
- Publication Type:Journal Article
- Keywords:
IL-38;
cardiomyocyte;
exosomes;
miR-1275;
sepsis
- MeSH:
Apoptosis/drug effects*;
MicroRNAs/metabolism*;
Myocytes, Cardiac/metabolism*;
Animals;
Lipopolysaccharides;
Rats;
Exosomes/metabolism*;
Up-Regulation;
Interleukins/metabolism*;
Lymphocytes/cytology*;
Cells, Cultured;
Signal Transduction;
Coculture Techniques;
Phosphatidylinositol 3-Kinases/metabolism*;
Rats, Sprague-Dawley;
Humans;
Proto-Oncogene Proteins c-akt/metabolism*
- From:
Journal of Southern Medical University
2025;45(8):1608-1615
- CountryChina
- Language:Chinese
-
Abstract:
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.
