Gata-4-overexpressed bone marrow mesenchymal stem cell secreted exosomes promote bone marrow mesenchymal stem cell differentiation into cardiomyocyte-like cells / 中国组织工程研究

ABSTRACT

BACKGROUND: Preliminary study has shown that overexpression of GATA-4-overexpressing bone marrow mesenchymal stem cell (BMSCs) exosomes (BMSCsGATA-4-exosome) can promote BMSCs differentiate into cardiomyocytes, indicating it can repair myocardial infarction. Additionally, high expression of miRNA-673-5p is observed in miRNA-673-5p BMSCsGATA-4-exosome and focal myocardium of myocardial infarction, which involve in cell differentiation, suggesting that miRNA-673-5p may be a key molecular of BMSCsGATA-4-exosome for repairing myocardial infarction. OBJECTIVE: To investigate the molecular regulatory network of BMSCsGATA-4-exosomes that promotes BMSCs differentiation into cardiomyocyte-like cells. METHODS: miR-673-5p-mimic was added to the BMSCs culture system as an experimental group (BMSCsmiR-330-3p-mimic ). BMSCsGATA-4, BMSCsGATA-4-empty vector, BMSCs and BMSCsGATA-4-miR-673-5p-inhibitor groups were set as confounding factor control groups. The exosomes and myocardial cells secreted by each group were co-cultured for 24 hours. The expression levels of myocardium specific molecules α-actin, Desmin, cTnT and Cx43 were detected by immunofluorescence and RT-PCR. The expression levels of the corresponding miRNA-673-5p target genes TSC-1, ERK1/2 and Mef2c were detected through western blot assay based on the prediction results of the microRNA target gene. RESULTS AND CONCLUSION: The BMSCsmiR-673-5p-mimic-exosome+BMSCs culture group had the highest α-actin, Desmin, cTnT and Cx43 levels (P < 0.05), and the lowest TSC-1 expression (P < 0.05). In summary, BMSCsGATA-4-exosome inhibits the expression of TSC-1 via miRNA-673-5p to promote BMSCs differentiation into cardiomyocyte-like cells.