MiR-124 suppresses the chemotactic migration of rat mesenchymal stem cells toward HGF by downregulating Wnt/beta-catenin signaling
MiR-124 suppresses the chemotactic migration of rat mesenchymal stem cells toward HGF by downregulating Wnt/beta-catenin signaling
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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 的趋化迁移
DOI：
10.1016/j.ejcb.2016.06.005
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发表时间：
2016
影响因子：
6.6
通讯作者：
Zhang Huanxiang
中科院分区：
文献类型：
--
作者：
Yue Qing;Zhang Yu;Li Xianyang;He Lihong;Hu Ya'nan;Wang Xianyao;Xu Xiaojing;Shen Yixin;Zhang Huanxiang
间充质干细胞（MSCs）具有修复多种损伤的成体组织的潜力。骨髓间充质干细胞的迁移能力是骨髓间充质干细胞移植治疗效果的重要决定因素。MicroRNAs （miRNAs）越来越多地参与调节MSCs的迁移。在这里，我们发现miR-124在肝细胞生长因子（HGF）处理的大鼠间充质干细胞（rMSCs）中表达下调。过表达miR-124可显著降低rMSCs向HGF的趋化迁移，而抑制内源性miR-124可促进趋化迁移。进一步研究发现，miR-124直接靶向编码Wnt/β-catenin信号通路受体和共受体的FZD4和LRP6，从而降低了该信号通路的活性。与此一致的是，通过LiCl和ΔN89β-catenin激活Wnt/β-catenin信号通路恢复了miR-124对rmsc向HGF趋化迁移的抑制作用，而通过FH535抑制Wnt/β-catenin信号通路则取消了miR-124抑制剂增强的趋化反应。总之，我们的研究表明miR-124通过靶向FZD4和LRP6下调Wnt/β-catenin信号，从而抑制rmsc向HGF的趋化迁移。
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.