title: MiR-499 induces cardiac differentiation of rat mesenchymal stem cells through wnt/β-catenin signaling pathway.
abstract: OBJECTIVE
  To test the hypothesis that over-expressing miR-499 in rat bone marrow-derived mesenchymal stem cells (BM-MSCs) induces them to differentiate into cardiomyocyte-like cells through the wnt/β-catenin signaling pathway.
  
  
  METHODS
  Rat BM-MSCs were infected with lentiviral vectors bearing miR-499. The expression of cardiac-specific markers, NKx2.5, GATA4, MEF2C, and cTnI in these cells were examined by rtPCR or Western blot analysis and the activity of the wnt/β-catenin signaling pathway was evaluated by measuring the phosphorylation status of β-catenin.
  
  
  RESULTS
  Over-expression of miR-499 in rat BM-MSCs increased the expression of cardiac-specific genes, such as NKx2.5, GATA4, MEF2C, and cTnI and decreased the ratio of phosphorylated/dephosphorylated β-catenin in the wnt/β-catenin signaling pathway, thus activating the pathway. Knocking down the expression of Dvl, an adaptor molecule in the wnt/β-catenin signaling, partially blocked the role of the miR-499 and decreased those cardiac-specific genes.
  
  
  CONCLUSIONS
  Over-expression of miR-499 in rat BM-MSCs induces them toward cardiac differentiation through the activating the wnt/β-catenin signal pathway.
authors.affiliation: Department of Cardiology, The Second Affiliated Hospital of Harbin Medical University, Key Laboratory of Myocardial Ischemia Mechanism and Treatment (Harbin Medical University), Ministry of Education, Baojian Road, Harbin, Heilongjiang Province 150081, PR China.
authors.forename: Lu-lu
authors.initials: LL
authors.lastname: Zhang
authors.forename: Jing-jin
authors.initials: JJ
authors.lastname: Liu
authors.forename: Fang
authors.initials: F
authors.lastname: Liu
authors.forename: Wen-hua
authors.initials: WH
authors.lastname: Liu
authors.forename: Yong-shun
authors.initials: YS
authors.lastname: Wang
authors.forename: Bin
authors.initials: B
authors.lastname: Zhu
authors.forename: Bo
authors.initials: B
authors.lastname: Yu
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology*; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000166:cytology*; D051381:Rats; D015398:Signal Transduction; D051153:Wnt Proteins / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism*
chemical_list: C558425:MIRN499 microRNA, rat; D035683:MicroRNAs; D051153:Wnt Proteins; D051176:beta Catenin