Pioglitazone alleviates oxygen and glucose deprivation-induced injury by up-regulation of miR-454 in H9c2 cells

Objective(s): Pioglitazone, an anti-diabetic agent, has been widely used to treat type II diabetes. However, the effect of pioglitazone on myocardial ischemia reperfusion injury (MIRI) is still unclear. Herein, the objective of this study is to learn about the regulation and mechanism of pioglitazone effects on oxygen glucose deprivation (OGD)-induced myocardial cell injury. Materials and Methods: A cellular injury model of OGD-treated H9c2 cells in vitro was constructed to simulate ischemic/reperfusion (I/R) injury. Then, various concentrations of pioglitazone (0, 2.5, 5, 7.5 and 10 μM) were used for the treatment of H9c2 cells, and CCK-8, flow cytometry and western blot assays were performed to examine cell viability, apoptosis, and the protein levels of factors involved in cell cycle and apoptosis in OGD-treated cells. MiR-454 inhibitor was used to suppress miR-454 expression, and whether miR-454 was involved in regulating OGD-induced cell injury was studied. Two key signal pathways were examined to uncover the underlying mechanism. Results: OGD reduced cell proliferation and induced apoptosis in H9c2 cells (P<0.05, P<0.01 or P< 0.001). OGD-induced injury was significantly attenuated by pioglitazone at the concentration of 5 μM. Additionally, pioglitazone significantly up-regulated miR-454 expression in OGD-injured cells (P< 0.05 or P< 0.01). MiR-454 suppression declined the protective effect of pioglitazone on OGD-injured H9c2 cells (P<0.05 or P< 0.01). Besides, pioglitazone activated PI3K/AKT and ERK/MAPK pathways via upregulating miR-454. Conclusion: Pioglitazone protected H9c2 cells against OGD-induced injury through up-regulating miR-454, indicating a novel therapeutic strategy for treatment of MIRI.