Effect of miR-412-5p-loaded exosomes in H9c2 cardiomyocytes via the MAPK pathway.

ABSTRACT

Objectives: MicroRNAs (miRNAs) are small non-coding RNAs that function in all biological processes. Recent findings suggest that exosomes, which are small vesicles abundantly secreted by various cell types, can transport miRNAs to target cells. Here, we elucidated the effect of miRNA-loaded exosomes on lipopolysaccharide (LPS)-induced inflammation in H9c2 cardiomyocytes. Materials and Methods: Exosomes were isolated from mesenchymal stem cells (MSC) and loaded with miR-412-5p. Additionally, the effect of the miR-412-5p-loaded exosomes on LPS-induced inflammation in H9c2 cardiomyocytes was evaluated by assessing the levels of nitric oxide (NO), reactive oxygen species (ROS), and prostaglandin E2 (PGE2). The expression of cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), inflammatory cytokines, and mitogen-activated protein kinase (MAPK) signaling factors was evaluated using reverse transcription-quantitative PCR and western blotting. Results: miR-412-5p-loaded exosomes inhibited LPS-induced secretion of inflammatory mediators (NO, PGE2, and ROS), pro-inflammatory cytokines (IL-1ß and IL-6), and COX-2 and iNOS expression. Additionally, miR-412-5p-loaded exosomes significantly decreased the expression of MAPK signaling molecules, including p-extracellular signal-regulated kinase (ERK), p-p38, and p-Jun kinase (JNK), in H9c2 cardiomyocytes. Conclusion: These findings showed that miR-412-5p-loaded exosomes ameliorated LPS-induced inflammation in H9c2 cardiomyocytes by inhibiting COX-2 and iNOS expression, inflammatory mediators, and pro-inflammatory cytokines via the MAPK pathway. The findings indicate that miR-412-5p-loaded exosomes may be effective for the prevention of myocardial injury.