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

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• 作者：Lu-lu Zhang ; Jing-jin Liu ; Fang Liu ; Wen-hua Liu ; Yong-shun Wang ; Bin Zhu ; Bo Yu ; ^{yubohmu@163.com}
• 关键词：MiR-499 ; Mesenchymal stem cells ; Cardiac differentiation ; wnt/尾-catenin signaling pathway
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：2012
• 期刊代码：159_0006291x
• 类别：bio
• 出版时间：20 April, 2012
• 卷：420
• 期：4
• 页码：875-881
• 文件大小：532 K

摘要

Objective

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/尾-catenin signaling pathway.

Methods

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/尾-catenin signaling pathway was evaluated by measuring the phosphorylation status of 尾-catenin.

Results

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 尾-catenin in the wnt/尾-catenin signaling pathway, thus activating the pathway. Knocking down the expression of Dvl, an adaptor molecule in the wnt/尾-catenin signaling, partially blocked the role of the miR-499 and decreased those cardiac-specific genes.

Conclusion

Over-expression of miR-499 in rat BM-MSCs induces them toward cardiac differentiation through the activating the wnt/尾-catenin signal pathway.