MiR-499 induces cardiac differentiation of rat mesenchymal stem cells through wnt/β-catenin signaling pathway

• Published in: Biochemical and biophysical research communications Vol. 420; no. 4; pp. 875 - 881
• Main Authors: Zhang, Lu-lu, Liu, Jing-jin, Liu, Fang, Liu, Wen-hua, Wang, Yong-shun, Zhu, Bin, Yu, Bo
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 20.04.2012
• Subjects: Animals; beta Catenin - metabolism; Cardiac differentiation; Cell Differentiation - genetics; Cell Differentiation - physiology; Mesenchymal stem cells; Mesenchymal Stromal Cells - cytology; MicroRNAs - genetics; MicroRNAs - metabolism; MiR-499; Myocytes, Cardiac - cytology; Rats; Signal Transduction; Wnt Proteins - metabolism; wnt/β-catenin signaling pathway; MiR-499; wnt/β-catenin signaling pathway; Cardiac differentiation; Mesenchymal stem cells
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2012.03.092

► Test cardiac differentiation role of miR-499 just of MSCs for the first time. ► Test cardiac differentiation in MSCs just by miR-499 for the first time. ► Wnt/β-catenin role in cardiac differentiation induced by miR-499 for the first time. To test the hypothesis that over-expressing miR-499 in rat bone marrow-derived mesenchymal stem cells (BM-MSCs) induces them to differentiate into cardiomyocyte-like cells through the wnt/β-catenin signaling pathway. Rat BM-MSCs were infected with lentiviral vectors bearing miR-499. The expression of cardiac-specific markers, NKx2.5, GATA4, MEF2C, and cTnI in these cells were examined by rtPCR or Western blot analysis and the activity of the wnt/β-catenin signaling pathway was evaluated by measuring the phosphorylation status of β-catenin. Over-expression of miR-499 in rat BM-MSCs increased the expression of cardiac-specific genes, such as NKx2.5, GATA4, MEF2C, and cTnI and decreased the ratio of phosphorylated/dephosphorylated β-catenin in the wnt/β-catenin signaling pathway, thus activating the pathway. Knocking down the expression of Dvl, an adaptor molecule in the wnt/β-catenin signaling, partially blocked the role of the miR-499 and decreased those cardiac-specific genes. Over-expression of miR-499 in rat BM-MSCs induces them toward cardiac differentiation through the activating the wnt/β-catenin signal pathway.