Conclusion
Pioglitazone protected H9c2 cells against OGD-induced injury through up-regulating miR-454, indicating a novel therapeutic strategy for treatment of MIRI.
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 up-regulating miR-454.