Human umbilical cord mesenchymal stem cells-derived exosomes transfers microRNA-19a to protect cardiomyocytes from acute myocardial infarction by targeting SOX6
Lin Huang, Yang Lü, Ying Ding, Xinghua Jiang, Zhen Xia, Zhigang You
Abstract
Exosomes secreted by human umbilical cord mesenchymal stem cells (hucMSCs) protect cardiomyocytes from anoxia-reoxygenation injury. But the mechanism of hucMSC-exo-microRNA (miR)-19a in acute myocardial infarction (AMI) remains unclear. For this study, cardiac function related indicators, inflammatory factors and markers of myocardial injury, cardiomyocyte injury, infarct size, and apoptosis were detected in vivo experiments. The gain-and loss-of function was performed to evaluate the effects of hucMSC-exo with down/upregulated miR-19a on AMI rats and hypoxic H9C2 cells. Western blot analysis was used to detect levels of AKT/JNK3/caspase-3 axis-related proteins. Consequently, hucMSC-exo alleviated AMI and inhibited cardiomyocyte apoptosis. miR-19a was downregulated in AMI tissues and cells, and increased after hucMSC-exo treatment. miR-19a knockdown in hucMSC-exo impaired the protective role of hucMSC-exo alone in the AMI damage. SOX6 is a target gene of miR-19a and its inhibition lightened hypoxic damage of H9C2 cells. SOX6 knockdown together with miR-19a inhibition in hucMSC-exo activated AKT and inhibited JNK3/caspase-3 axis. Taken together, hucMSC-exo protected cardiomyocytes from AMI injury by transferring miR-19a, targeting SOX6, activating AKT, and inhibiting JNK3/caspase-3 activation. This study may provide new understanding for AMI treatment.