Mesenchymal stem cells (MSCs) exhibit the potential to repair a wide variety of injured adult tissues. The migration capability of MSCs is an important determinant of the efficiency of MSC transplant therapy. MicroRNAs (miRNAs) are increasingly implicated in regulating the migration of MSCs. Herein, we show that the expression of miR-124 was downregulated in rat MSCs (rMSCs) treated with hepatocyte growth factor (HGF). Overexpression of miR-124 significantly reduced the chemotactic migration of rMSCs toward HGF, while inhibition of endogenous miR-124 promoted the chemotactic migration. A further study revealed that miR-124 directly targeted FZD4 and LRP6, which encode a receptor and co-receptor of the Wnt/β-catenin signaling pathway, respectively, thus reducing the activity of this signaling. Consistently, activation of the Wnt/β-catenin signaling pathway by LiCl and ΔN89β-catenin rescued the inhibitory effect of miR-124 on the chemotactic migration of rMSCs toward HGF, while inhibition of Wnt/β-catenin signaling by FH535 abrogated the enhanced chemotactic response achieved by the miR-124 inhibitor. Collectively, our study demonstrates that miR-124 downregulates Wnt/β-catenin signaling via targeting FZD4 and LRP6 and thus suppresses the chemotactic migration of rMSCs toward HGF.

中文翻译：

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MiR-124通过下调Wnt /β-catenin信号传导抑制大鼠间充质干细胞向HGF趋化迁移。

间充质干细胞（MSCs）具有修复多种受损成年组织的潜力。MSC的迁移能力是MSC移植治疗效率的重要决定因素。微小RNA（miRNA）越来越涉及调控MSC的迁移。在本文中，我们显示在用肝细胞生长因子（HGF）处理的大鼠MSC（rMSC）中，miR-124的表达下调。miR-124的过表达显着降低了rMSCs向HGF的趋化迁移，而抑制内源性miR-124则促进了趋化迁移。进一步的研究表明，miR-124直接靶向FZD4和LRP6，它们分别编码Wnt /β-catenin信号通路的受体和共受体，从而降低了该信号传导的活性。始终如一 LiCl和ΔN89β-catenin对Wnt /β-catenin信号通路的激活挽救了miR-124对rMSCs向HGF趋化迁移的抑制作用，而FH535对Wnt /β-catenin信号传导的抑制作用消除了所实现的增强的趋化反应。由miR-124抑制剂提供。总体而言，我们的研究表明miR-124通过靶向FZD4和LRP6下调Wnt /β-catenin信号传导，从而抑制rMSC向HGF的趋化迁移。