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

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. J. Cell. Biochem. 117: 1370–1383, 2016. © 2015 Wiley Periodicals, Inc.