Inhibition of miR-182-5p attenuates ROS and protects against myocardial ischemia-reperfusion injury by targeting STK17A

Reperfusion therapy for acute myocardial infarction inevitably leads to ischemia-reperfusion (I/R) injury. A number of miRNAs are reported to be involved in I/R injury. This study aims to investigate the role and underlying mechanism of miR-182-5p in I/R injury. An in vivo model of I/R-induced rat myocardial injury and an in vitro model of H/R H9c2 cells were established to investigate the role and mechanism of miR-182-5p in I/R injury. The myocardial infarct size was determined by TTC staining. The serum CK-MB level was determined by ELISA kit. The miR-182-5p inhibitors or mimics were used to down-regulate or up-regulate its expression. The apoptosis and ROS were detected by flow cytometry. The expression of the proteins was detected by western blot. The binding of STK17A and miR-182-5p was validated by dual-luciferase reporter assay. The miR-182-5p was confirmed to be highly expressed in I/R injury rats and H/R H9c2 cells. Inhibition of miR-182-5p significantly reduced the infarct size and decreased the serum CK-MB level of I/R rats, and significantly reduced the ROS level but increased the level of MnSOD and catalase. While, an opposite effect was observed in the miR-182-5p mimics group. Furthermore, our results suggested that miR-182-5p targeted STK17A, and TK17A knockdown significantly increased the apoptotic rate and ROS level. The inhibitory effect of miR-182-5p inhibitors on apoptotic rate, ROS, MnSOD, and catalase levels were abrogated by siSTK17A. These results indicate that miR-182-5p regulates the apoptosis and ROS and protects against myocardial I/R injury by targeting STK17A.

Automated summary

This study revealed the important regulatory role of miR-182-5p in ischemia-reperfusion injury, by targeting STK17A to regulate myocardial cell apoptosis and oxidative stress response, thereby protecting the myocardium from I/R injury.