Related Experiment Video
Updated: Dec 4, 2025
In Vivo Nanovector Delivery of a Heart-specific MicroRNA-sponge
Published on: June 15, 2018
MicroRNA-338 in MSCs-derived exosomes inhibits cardiomyocyte apoptosis in myocardial infarction
1Cardiology Department of Integrated Traditional Chinese and Western Medicine, China-Japan Friendship Hospital, Beijing, China. drjh68@163.com.
Objective:
Myocardial infarction (MI) is caused by myocardial ischemia and hypoxia, which causes irreversible damage to the myocardium and seriously endangers human health. Exosomes are small, monolayer-structured extracellular vesicles that transport proteins, lipids, mRNAs, and miRNAs between cells. Mesenchymal stem cells (MSCs) can secrete a large number of exosomes and play a role in many pathophysiological processes. The purpose of this paper was to investigate the role of exosomal microRNA-338 (miR-338) in MI and its underlying mechanism of action.
Materials And Methods:
We transfected rat bone marrow-derived MSCs with miR-338 mimic or negative control and extracted exosomes secreted by MSCs. Expression of miR-338 in MSCs, exosomes, and H9c2 cells co-cultured with exosomes was detected by PCR. Then, we treated H9c2 cells with H2O2. We transfected miR-338 inhibitor into H9c2 cells co-cultured with exosomes to further study the function of miR-338. Apoptosis of H9c2 cells were observed by Western blot, flow cytometry, and cell staining. We also established a MI rat model to study the function in vivo and injected exosomes in the myocardium. Seven days later, we used echocardiography to detect the heart function of rats.
Results:
MiR-338 was upregulated in MSCs transfected with miR-338 mimic, exosomes, and H9c2 cells co-cultured with exosomes. When H9c2 cells were co-cultured with exosomes overexpressing miR-338, the expression of Bax was decreased while the expression of Bcl-2 was increased, and the apoptosis rate was also decreased as shown in flow cytometry, and the amount of caspase3 fluorescence was also decreased. Cardiac function was markedly improved after intramyocardial injection of exosomes overexpressing miR-338 in rats. It was demonstrated using computational tools, Western blot, and Luciferase reporter gene experiments that miR-338 could regulate JNK pathway via targeting MAP3K2.
Conclusions:
Exosomal miR-338 can inhibit cardiomyocyte apoptosis and improve cardiac function in rats with myocardial infarction by regulating MAP3K2/JNK signaling pathway.
Insights
Exosomes carrying microRNA-338 (miR-338) protect heart function after myocardial infarction (MI). These exosomes reduce cardiomyocyte apoptosis by targeting the MAP3K2/JNK pathway, offering a potential therapeutic strategy for MI.
Area of Science:
- Cardiovascular Research
- Molecular Biology
- Cell Biology
Background:
- Myocardial infarction (MI) causes irreversible heart damage due to ischemia and hypoxia.
- Exosomes, secreted by mesenchymal stem cells (MSCs), are key intercellular communicators.
- MicroRNAs (miRNAs) within exosomes play critical roles in cellular functions.
Purpose of the Study:
- To investigate the role of exosomal microRNA-338 (miR-338) in myocardial infarction (MI).
- To elucidate the underlying mechanism of exosomal miR-338 action in MI.
- To assess the therapeutic potential of miR-338-enriched exosomes in a rat MI model.
Main Methods:
- MSCs were transfected to overexpress miR-338, and exosomes were isolated.
- H9c2 cells and a rat MI model were used to evaluate exosome function in vitro and in vivo.
- Apoptosis, cardiac function, and the MAP3K2/JNK pathway were analyzed using molecular and imaging techniques.
Main Results:
- Exosomes overexpressing miR-338 reduced H9c2 cell apoptosis by downregulating Bax and upregulating Bcl-2.
- Intramyocardial injection of miR-338-enriched exosomes significantly improved cardiac function in MI rats.
- miR-338 was identified to target MAP3K2, regulating the JNK signaling pathway.
Conclusions:
- Exosomal miR-338 demonstrates cardioprotective effects by inhibiting cardiomyocyte apoptosis.
- The MAP3K2/JNK signaling pathway is a key mediator of exosomal miR-338's therapeutic action.
- miR-338-loaded exosomes represent a promising therapeutic approach for myocardial infarction.
