title: Up-Regulation of miRNA-21 Expression Promotes Migration and Proliferation of Sca-1+ Cardiac Stem Cells in Mice.
abstract: BACKGROUND This 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 AND METHODS The 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. RESULTS Immunomagnetic 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. CONCLUSIONS Our 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.
authors.affiliation: Department of Cardiovascular Surgery, The Second Hospital of Shandong University, Jinan, Shandong, China (mainland).
authors.forename: Qingling
authors.initials: Q
authors.lastname: Zhou
authors.affiliation: Department of Cardiovascular Surgery, The Second Hospital of Shandong University, Jinan, Shandong, China (mainland).
authors.forename: Qiang
authors.initials: Q
authors.lastname: Sun
authors.affiliation: Department of Cardiovascular Surgery, The Second Hospital of Shandong University, Jinan, Shandong, China (mainland).
authors.forename: Yongshan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Cardiovascular Surgery, The Second Hospital of Shandong University, Jinan, Shandong, China (mainland).
authors.forename: Fei
authors.initials: F
authors.lastname: Teng
authors.affiliation: Department of Cardiovascular Surgery, The Second Hospital of Shandong University, Jinan, Shandong, China (mainland).
authors.forename: Jinhui
authors.initials: J
authors.lastname: Sun
mesh_terms: D000818:Animals; D000067696:Ataxin-1 / Q000096:biosynthesis* / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D002478:Cells, Cultured; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D009206:Myocardium / Q000166:cytology* / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
chemical_list: D000067696:Ataxin-1; C000593750:Atxn1 protein, mouse; C531950:MIRN21 microRNA, mouse; D035683:MicroRNAs