Up-Regulation of miRNA-21 Expression Promotes Migration and Proliferation of Sca-1+ Cardiac Stem Cells in Mice

Abstract

BackgroundThis study, by regulating the expression level of microRNA-21 (miRNA-21) in antigen-1+ (Sca-1+) cardiac stem cells (CSCs), examined the role of miRNA-21 in migration, proliferation, and differentiation of Sca-1+ CSCs, and explored the use of miRNA-21 in treatment of heart-related diseases in mice.Material/MethodsThe CSCs of 20 healthy 2-month-old C57BL/6 mice were collected in our study. Immunomagnetic beads were used to separate and prepare pure Sca-1+ CSCs, which were further examined by flow cytometry. The samples were assigned to 4 groups: the blank group, the miRNA-21 mimic group, the miRNA-21 inhibitor group, and the negative control (NC) group. Quantitative real-time polymerase chain reaction (qRT-PCR), Transwell chamber assay, and the methyl thiazolylte-trazolium (MTT) assay were performed. Reverse transcriptase-polymerase chain reaction (RT-PCR) was used to measure the expression levels of GATA-4, MEF2c, TNI, and β-MHC differentiation-related genes.ResultsImmunomagnetic separation results indicated that Sca-1+ CSCs accounted for more than 87.4% of CSCs. RT-PCR results also showed that the expression level of miRNA-21 of the miRNA-21 mimic group was higher than those of the other groups (all P<0.05). Compared to the NC and the blank group, the migration of Sca-1+ CSCs was more active in the miRNA-21 mimic group and less active in the miRNA-21 inhibitor group (all P<0.05). Moreover, compared to the blank group, the proliferation of Sca-1+ CSCs was enhanced in the miRNA-21 mimic group and inhibited in the miRNA-21 inhibitor group (all P<0.05). The results of RT-PCR indicated that neither miRNA-21 mimics nor miR-21 inhibitors influenced the gene expression levels of GATA-4, MEF2c, TNI, or β-MHC.ConclusionsOur study provides evidence that up-regulation of miRNA-21 can promote migration and proliferation of Sca-1+ CSCs to enhance the capacity of Sca-1+ CSCs to repair damaged myocardium, which may pave the way for therapeutic strategies directed toward restoring miRNA-21 function for heart-related diseases.

MicroRNA-21 ablation exacerbates aldosterone-mediated cardiac injury, remodeling, and dysfunction

“…It is important to highlight that in the above mentioned studies related to the miR-21/Sprouty axis, miR-21plays a cardiac deleterious role, whereas in our experimental model as in many other ones (17,18,25,43,62,63,65,75,77,84,88,100,104,109) miR-21 plays a protective role. Consequently, the interpretation of the role of Sprouty proteins as mediators of miR-21 actions is more difficult and would require further studies.…”

“…In animal experimental models, cardiac miR-21 has been shown to be upregulated by thoracic aortic banding (16, 75-77, 84, 89), ischemia/reperfusion (71), ischemic preconditioning (18,28), and heat shock (104) as well as in transgenic mice expressing activated calcineurin A (CnA), in the heart (89) and in the border zone of myocardial infarct (25,64,90,108), in a model of pulmonary insufficiency and stenosis (67) and in a model of diabetic nephropathy (95). Despite multiple studies, the role of miR-21 in cardiac pathophysiology remains highly controversial, with a plethora of studies suggesting that this particular miRNA can be either deleterious (1,5,14,16,32,38,44,48,63,66,86,95,108) or beneficial (17,18,25,43,62,63,65,75,77,84,88,100,104,109) in cardiac injury.…”

Non-Coding RNAs in Stem Cell Regulation and Cardiac Regeneration: Current Problems and Future Perspectives

“…It has been demonstrated to regulate stem cell migration and proliferation in vitro [53]. In a murine model of AMI, a single injection of miR-21-enriched exosomes induced angiogenesis and preserved the wall thickness and LVF [54].…”

Study on the Mechanism of Mirna-21 Affecting the Differentiation of Bone Marrow Mesenchymal Stem Cells into Cardiomyocyte-Like Cells By Targeting Ajuba / Isl1 Axis

“…Ajuba overexpression (ajuba OE) and interference with ajuba (ajuba KD) infected BMSC. CTnI was detected by immuno uorescence to observe the differentiation ability of into cardiac myoid cells MiRNA-21 is involved in the proliferation, apoptosis and differentiation of a variety of cells [3][4][5][6][7][8][9][10], and related target genes and possible related pathways are reported [11,12,13] However, its exact mechanism is not clear. In order to improve the role of BMSC in the treatment of ischemic diseases, especially coronary heart disease, it is necessary to carry out further exploration.…”