JCK E-Oral Presentation 1 (II-JCKEOP01)

[II-JCKEOP01-01] Differentiation of mesenchymal stem cells into cardiomyocytes is regulated by miRNA-1-2 via WNT signaling pathway

^○Xing Shen¹, Bo Pan¹, Huiming Zhou¹, Lingjuan Liu¹, Tiewei Lv¹, Jing Zhu¹,Xupei Huang², Jie Tian¹ (1.Department of Cardiology, Chongqing Medical University ,Chongqing-City, China, 2.Department of Biomedical Science, Charlie E. Schmidt College of Medicine, Florida Atlantic University, Boca Raton, FL, USA)

Objective: To investigate the role of miR1-2 in differentiation of mouse BMSCs into cardiomyocyte-like cells and reveal the involved signaling pathways in the procedure. Methods: Mouse BMSCs were treated with miR1-2 and 5-azacytine (5-aza). The expression of cardiac cell markers: NKx2.5, cTnI and GATA4 in BMSCs were examined by qPCR, The apoptosis rate was detected by flow cytometry and the activity of the Wnt/β-catenin signaling pathway was evaluated by measuring the upstream protein of this signaling pathway. Results: After overexpression of miR1-2 in mouse BMSCs, the apoptosis rate was significantly lower than the 5-aza group, While the expressions of cardiac-specific genes: such as Nkx2.5 ,cTnI and GATA4 were significantly increased compared to the control group and the 5-aza group. Meanwhile, overexpression of miR1-2 in mouse BMSCs enhanced the expression of wnt11, JNK, β-catenin and TCF in the Wnt/β-catenin signaling pathway. Use of LGK-974, an inhibitor of Wnt/β-catenin signaling pathway, significantly reduced the expression of cardiac-specific genes and partially blocked the role of the miR1-2. Conclusion: Overexpression of miR1-2 in mouse BMSCs can induce them toward cardiomyocyte differentiation via the activation of the Wnt/β-catenin signaling pathway. Comparing with 5-aza, miR1-2 induced differentiation of BMSCs into cardiomyocytes is stronger and safer.