GATA-4-overexpressed bone marrow mesenchymal stem cell secreted
exosomes promote bone marrow mesenchymal stem cell differentiation into
cardiomyocyte-like cells

doi:10.3969/j.issn.2095-4344.2056

Abstract

Abstract:

BACKGROUND: Preliminary study has shown that overexpression of GATA-4-overexpressing bone marrow mesenchymal stem cell (BMSCs) exosomes (BMSCs^GATA-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 BMSCs^GATA-4-exosome and focal myocardium of myocardial infarction, which involve in cell differentiation, suggesting that miRNA-673-5p may be a key molecular of BMSCs^GATA-4-exosome for repairing myocardial infarction.

OBJECTIVE: To investigate the molecular regulatory network of BMSCs^GATA-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 (BMSCs^{miR-330-3p-mimic}). BMSCs^GATA-4, BMSCs^{GATA-4-empty vector}, BMSCs and BMSCs^{GATA-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 BMSCs^{miR-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, BMSCs^GATA-4-exosome inhibits the expression of TSC-1 via miRNA-673-5p to promote BMSCs differentiation into cardiomyocyte-like cells.

Key words: miRNA-673-5p, TSC-1, GATA-4, exosomes, mouse, bone marrow mesenchymal stem cells

CLC Number:

He Jigang, Wang Zihao, Xie Qiaoli, Li Hongrong, Yan Dan, Li Yongwu. GATA-4-overexpressed bone marrow mesenchymal stem cell secreted exosomes promote bone marrow mesenchymal stem cell differentiation into cardiomyocyte-like cells[J]. Chinese Journal of Tissue Engineering Research, 2020, 24(19): 2965-2971.

Figures/Tables 6

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