PI3K/AKT/GSK3β regulatory axis in bone mesenchymal stem cells initiates diabetic myocardial infarction via miR-142-3p

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.