Overexpressed GATA-4 bone marrow-derived mesenchymal stem cell exosomes improve myocardial infarction via miRNA-673-5p/Tsc-1 molecular axis / 医学研究生学报

ABSTRACT

ObjectiveExosomes secreted by BMSC overexpressing GATA-4 gene (BMSCGATA-4-exosome) can promote the differentiation of BMSC into cardiomyocyte-like cells, thereby improve cardiac function after myocardial infarction. However, the molecular mechanism of BMSCGATA-4-exosome in cardiomyocyte-like cell differentiation is unknown. The effect of the secretion of BMSCGATA-4 exosome from bone marrow mesenchymal stem cells (BMSC) in the differentiation of stem cells into cardiomyocytes was determined in miRNA-673-5p/Tsc-1 axis dependent manner.MethodsMouse models of myocardial infarction were established and divided into seven groups. Simulation group (BMSCmiR-673-5p-mimic exosome), inhibition group (BMSCmiR-673-5p-inhibitor exosome), GATA-4 group (BMSCGATA-4 exosome), empty vector group (BMSCempty vector exosome）, and BMSC group (BMSC exosome) were injected into the tail vein for 48 h, and the untreated and normal mice were used as the control group. Cardiac ultrasound was used to detect cardiac function in each group. miRNA-673-5p expression in myocardial infarction was detected using real-time polymerase chain reaction (RT-PCR). The myocardial tissues were extracted from the same myocardial infarction site. Myocardial-specific molecules, such as α-actin, Desmin, cTnT, and Cx43, were detected using RT-PCR. Western blot was used to determine the expression of the corresponding target gene of miRNA-673-5p, Tsc-1, Erk1/2, and Mef2c proteins.ResultsThe simulation group wan shown the most significantly improved myocardial function (P<0.05) with an expression peak of miRNA-673-5p in cardiomyocytes (P<0.05). The highest content of myocardial-specific molecules including α-actin, Desmin, cTnT, and Cx43 was found in the simulation group. The simulation group had the lowest expression of Tsc-1 in cardiomyocytes (P<0.05).ConclusionOverexpressed BMSCGATA-4 exosomes inhibit Tsc-1 expression through miRNA-673-5p to improve cardiac function during myocardial infarction.