MiR-221 and miR-26b Regulate Chemotactic Migration of MSCs Toward HGF Through Activation of Akt and FAK
MiR-221 and miR-26b Regulate Chemotactic Migration of MSCs Toward HGF Through Activation of Akt and FAK
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MiR-221 和 miR-26b 通过激活 Akt 和 FAK 调节 MSC 向 HGF 的趋化迁移
DOI：
10.1002/jcb.25428
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发表时间：
2016
影响因子：
4
通讯作者：
Zhang Huanxiang
中科院分区：
文献类型：
--
作者：
Zhu Aisi;Kang Naixin;He Lihong;Li Xianyang;Xu Xiaojing;Zhang Huanxiang
间充质干细胞（MSCs）的趋化迁移是其在基于细胞的治疗中应用的基础，但对其定向迁移的分子机制知之甚少。MicroRNAs （miRNAs）参与多种细胞过程的调控。然而，它们在调节间充质干细胞对肝细胞生长因子（HGF）的反应中的作用尚不明确。在这里，我们发现microRNA‐221 （miR‐221）和microRNA‐26b （miR‐26b）在HGF作用下的MSCs中上调。miR‐221或miR‐26b的过表达通过激活PI3K/Akt信号通路增强MSC迁移。第十号染色体上缺失的磷酸酶和紧张素同源物（PTEN）被确定为miR‐221和miR‐26b的潜在靶标；miR‐221或miR‐26b的过表达降低了PTEN mRNA和蛋白水平的表达。miR - 221或miR - 26b在MSCs中的过度表达增加了局灶黏附激酶（FAK）的磷酸化，FAK是PTEN的下游效应物，通过局灶黏附（FAs）的组装和分布调节细胞迁移，并且更多的点状FAs位于这些细胞的周围。改变miR - 221或miR - 26b的表达会影响MSCs向HGF的定向迁移。miR - 221或miR - 26b的抑制抑制了Akt和FAK的磷酸化，上调了PTEN的表达，HGF处理部分恢复了PTEN的表达。总之，这些结果表明miR - 221和miR - 26b参与调节MSCs对HGF的趋化反应。j .细胞。中国生物医学工程学报，2016,31(2):369 - 369。©2015 Wiley期刊公司
The chemotactic migration of mesenchymal stem cells (MSCs) is fundamental for their use in cell‐based therapies, but little is known about the molecular mechanisms that regulate their directed migration. MicroRNAs (miRNAs) participate in the regulation of a large variety of cellular processes. However, their roles in regulating the responses of MSCs to hepatocyte growth factor (HGF) remain elusive. Here, we found that microRNA‐221 (miR‐221) and microRNA‐26b (miR‐26b) were upregulated in MSCs subjected to HGF. Overexpression of miR‐221 or miR‐26b enhanced MSC migration through activation of PI3K/Akt signaling. Phosphatase and tensin homolog deleted on chromosome ten (PTEN) was identified as a potential target of miR‐221 and miR‐26b; overexpression of miR‐221 or miR‐26b decreased PTEN expression at both mRNA and protein levels. Overexpression of miR‐221 or miR‐26b in MSCs increased the phosphorylation of focal adhesion kinase (FAK), a downstream effector of PTEN, which regulates cell migration through assembly and distribution of focal adhesions (FAs), and more dot‐like FAs were localized at the periphery of these cells. Altering miR‐221 or miR‐26b expression influenced the directed migration of MSCs toward HGF. Inhibition of miR‐221 or miR‐26b suppressed the phosphorylation of Akt and FAK and upregulated PTEN expression, which was partly restored by HGF treatment. Collectively, these results demonstrate that miR‐221 and miR‐26b participate in regulating the chemotactic response of MSCs toward HGF. J. Cell. Biochem. 117: 1370–1383, 2016. © 2015 Wiley Periodicals, Inc.