title: MiR-23b and miR-199a impair epithelial-to-mesenchymal transition during atrioventricular endocardial cushion formation.
abstract: BACKGROUND
  Valve development is a multistep process involving the activation of the cardiac endothelium, epithelial-mesenchymal transition (EMT) and the progressive alignment and differentiation of distinct mesenchymal cell types. Several pathways such as Notch/delta, Tgf-beta and/or Vegf signaling have been implicated in crucial steps of valvulogenesis. We have previously demonstrated discrete changes in microRNAs expression during cardiogenesis, which are predicted to target Bmp- and Tgf-beta signaling. We now analyzed the expression profile of 20 candidate microRNAs in atrial, ventricular, and atrioventricular canal regions at four different developmental stages.
  
  
  RESULTS
  qRT-PCR analyses of microRNAs demonstrated a highly dynamic and distinct expression profiles within the atrial, ventricular, and atrioventricular canal regions of the developing chick heart. miR-23b, miR-199a, and miR-15a displayed increased expression during early AVC development whereas others such as miR-130a and miR-200a display decreased expression levels. Functional analyses of miR-23b, miR-199a, and miR-15a overexpression led to in vitro EMT blockage. Molecular analyses demonstrate that distinct EMT signaling pathways are impaired after microRNA expression, including a large subset of EMT-related genes that are predicted to be targeted by these microRNAs.
  
  
  CONCLUSIONS
  Our data demonstrate that miR-23b and miR-199a over-expression can impair atrioventricular EMT.
authors.affiliation: Cardiovascular Research Group, Department of Experimental Biology, Faculty of Experimental Sciences, University of Jaén, Jaén, Spain.
authors.forename: Fernando
authors.initials: F
authors.lastname: Bonet
authors.affiliation: Cardiovascular Research Group, Department of Experimental Biology, Faculty of Experimental Sciences, University of Jaén, Jaén, Spain.
authors.forename: Ángel
authors.initials: Á
authors.lastname: Dueñas
authors.affiliation: Department of Anatomy and Embryology, Faculty of Medicine, University of Extremadura, Badajoz, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: López-Sánchez
authors.affiliation: Department of Anatomy and Embryology, Faculty of Medicine, University of Extremadura, Badajoz, Spain.
authors.forename: Virginio
authors.initials: V
authors.lastname: García-Martínez
authors.affiliation: Cardiovascular Research Group, Department of Experimental Biology, Faculty of Experimental Sciences, University of Jaén, Jaén, Spain.
authors.forename: Amelia E
authors.initials: AE
authors.lastname: Aránega
authors.affiliation: Cardiovascular Research Group, Department of Experimental Biology, Faculty of Experimental Sciences, University of Jaén, Jaén, Spain.
authors.forename: Diego
authors.initials: D
authors.lastname: Franco
mesh_terms: D000818:Animals; D002642:Chick Embryo; D058750:Epithelial-Mesenchymal Transition; D018507:Gene Expression Regulation, Developmental; D006321:Heart / Q000196:embryology*; D035683:MicroRNAs / Q000378:metabolism*
chemical_list: D035683:MicroRNAs
keywords: EMT; cardiac valve development; miR-199a; miR-23b