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. 2016 Jun;117(6):1370-83.
doi: 10.1002/jcb.25428. Epub 2015 Nov 24.

MiR-221 and miR-26b Regulate Chemotactic Migration of MSCs Toward HGF Through Activation of Akt and FAK

Aisi Zhu  1 , Naixin Kang  1 , Lihong He  1 , Xianyang Li  1 , Xiaojing Xu  1 , Huanxiang Zhang  1
Affiliations

MiR-221 and miR-26b Regulate Chemotactic Migration of MSCs Toward HGF Through Activation of Akt and FAK

Aisi Zhu et al. J Cell Biochem. 2016 Jun.

Abstract

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.

Keywords: PTEN; focal adhesion kinase (FAK); hepatocyte growth factor (HGF); mesenchymal stem cells (MSCs); miR-221 and miR-26b; migration.

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