title: MiR-124 suppresses the chemotactic migration of rat mesenchymal stem cells toward HGF by downregulating Wnt/β-catenin signaling.
abstract: 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.
authors.affiliation: Department of Cell Biology, Jiangsu Key Laboratory of Stem Cell Research, Medical College of Soochow University, Suzhou 215123, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Yue
authors.affiliation: Department of Orthopedics, the Second Affiliated Hospital of Soochow University, Suzhou Jiangsu, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Cell Biology, Jiangsu Key Laboratory of Stem Cell Research, Medical College of Soochow University, 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, 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, Suzhou 215123, China.
authors.forename: Ya'nan
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Department of Cell Biology, Jiangsu Key Laboratory of Stem Cell Research, Medical College of Soochow University, Suzhou 215123, China.
authors.forename: Xianyao
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Cell Biology, Jiangsu Key Laboratory of Stem Cell Research, Medical College of Soochow University, Suzhou 215123, China.
authors.forename: Xiaojing
authors.initials: X
authors.lastname: Xu
authors.affiliation: Department of Orthopedics, the Second Affiliated Hospital of Soochow University, Suzhou Jiangsu, China.
authors.forename: Yixin
authors.initials: Y
authors.lastname: Shen
authors.affiliation: Department of Cell Biology, Jiangsu Key Laboratory of Stem Cell Research, Medical College of Soochow University, Suzhou 215123, China. Electronic address: hzhang@suda.edu.cn.
authors.forename: Huanxiang
authors.initials: H
authors.lastname: Zhang
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics; D002633:Chemotaxis / Q000235:genetics; D015536:Down-Regulation; D057809:HEK293 Cells; D017228:Hepatocyte Growth Factor / Q000494:pharmacology*; D006801:Humans; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D035683:MicroRNAs / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D014162:Transfection; D060449:Wnt Signaling Pathway / Q000187:drug effects / Q000235:genetics*
chemical_list: C509207:MIRN124 microRNA, human; D035683:MicroRNAs; C540079:Mirn124 microRNA, mouse; D017228:Hepatocyte Growth Factor
keywords: Chemotactic migration; FZD4 and LRP6; Rat mesenchymal stem cells (rMSCs); Wnt/β-catenin signaling; miR-124