Published online Sep 20, 2025. doi: 10.5493/wjem.v15.i3.103948
Revised: March 12, 2025
Accepted: April 27, 2025
Published online: September 20, 2025
Processing time: 250 Days and 3.4 Hours
We aimed to identify the key proteins of miR-142-3p that regulate ferroptosis and ultimately control the downstream effectors of cardiomyocyte growth.
To investigate the role of miR-142-3p in regulating ferroptosis and its impact on diabetes-induced myocardial infarction via the PI3K/AKT/GSK3β pathway.
We constructed bones mesenchymal stem cells (BMCs) with low miR-142-3p expression and investigated its role using cell flow cytometry and western blotting (WB). A diabetes myocardial infarction model was established using streptozotocin and coronary artery ligation. The rats were divided into six groups (n = 15 per group): Control, sham surgery model, liraglutide intervention, BMCs intervention, and low miR-142-3p BMCs intervention. Interventions lasted for 7 days and BMCs injected for once. Blood glucose levels were monitored, and myocardial infarction improvements were assessed via electrocardiogra, general heart observation, staining techniques, and WB analysis.
We observed that miR-142-3p increased BMC apoptosis and affected AKT and GSK3β. The myocardial infarction drug, liraglutide, BMCs, and miR-142-3p low expression BMCs intervention showed improvement in differing degrees. The liraglutide and BMCs showed significant blood glucose reduction (0.05). BMCs increased the expression of PI3K, AKT, and GSK3, leading to an increase in the myocardial infarction intervention group, liraglutide, and BMCs intervention groups. The low miR-142-3p expression intervention with BMCs group had the lowest PI3K and AKT protein expression. Liraglutide improved ferroptosis markers (increased COX-2, decreased GPX4 and CHCHD6). Low miR-142-3p BMCs increased COX-2, GPX4, and CHCHD6. CCM3 and VEGFR2 expression increased in BMCs and low miR-142-3p groups, promoting myocardial repair, but decreased in the low miR-142-3p groups.
The preliminary results showed that the therapeutic mechanism of BMCs in diabetes myocardial infarction may involve miR-142-3p via the PI3K/AKT/GSK-3β axis, which jointly inhibits ferroptosis and programmed death.
Core Tip: This study demonstrated that using bones mesenchymal stem cells (BMCs) as an intervention can simultaneously reduce blood sugar levels and promote hypoxic myocardial recovery. However, when miR-142-3p expression in BMCs was low, there was a reduced therapeutic efficacy of BMCs and activation of PI3K/AKT/GSK-3β. The regulatory axis regulates changes in the protein expression levels of the ferroptosis-related genes GPX4/CHCHD6. These findings suggest that miR-142-3p via the PI3K/AKT/GSK-3β regulation axis that jointly inhibits ferroptosis, may be one of the therapeutic mechanisms of BMCs in diabetic myocardial infarction.