title: 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.
authors.affiliation: Department of Cell Biology, Jiangsu Key Laboratory of Stem Cell Research, Medical College of Soochow University, Ren Ai Road 199, Suzhou Industrial Park, Suzhou, 215123, China.
authors.forename: Aisi
authors.initials: A
authors.lastname: Zhu
authors.affiliation: Department of Cell Biology, Jiangsu Key Laboratory of Stem Cell Research, Medical College of Soochow University, Ren Ai Road 199, Suzhou Industrial Park, Suzhou, 215123, China.
authors.forename: Naixin
authors.initials: N
authors.lastname: Kang
authors.affiliation: Department of Cell Biology, Jiangsu Key Laboratory of Stem Cell Research, Medical College of Soochow University, Ren Ai Road 199, Suzhou Industrial Park, Suzhou, 215123, China.
authors.forename: Lihong
authors.initials: L
authors.lastname: He
authors.affiliation: Department of Cell Biology, Jiangsu Key Laboratory of Stem Cell Research, Medical College of Soochow University, Ren Ai Road 199, Suzhou Industrial Park, Suzhou, 215123, China.
authors.forename: Xianyang
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Cell Biology, Jiangsu Key Laboratory of Stem Cell Research, Medical College of Soochow University, Ren Ai Road 199, Suzhou Industrial Park, Suzhou, 215123, China.
authors.forename: Xiaojing
authors.initials: X
authors.lastname: Xu
authors.affiliation: Department of Cell Biology, Jiangsu Key Laboratory of Stem Cell Research, Medical College of Soochow University, Ren Ai Road 199, Suzhou Industrial Park, Suzhou, 215123, China.
authors.forename: Huanxiang
authors.initials: H
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D002633:Chemotaxis / Q000187:drug effects; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D017228:Hepatocyte Growth Factor / Q000494:pharmacology*; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects; D035683:MicroRNAs / Q000235:genetics*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction
chemical_list: C576526:MIRN221 microRNA, rat; C556274:MIRN26 microRNA, rat; D035683:MicroRNAs; D017228:Hepatocyte Growth Factor; D051417:Focal Adhesion Kinase 1; C496052:Ptk2 protein, rat; D051057:Proto-Oncogene Proteins c-akt
keywords: PTEN; focal adhesion kinase (FAK); hepatocyte growth factor (HGF); mesenchymal stem cells (MSCs); miR-221 and miR-26b; migration