title: Down-regulation of miR-23b induces phenotypic switching of vascular smooth muscle cells in vitro and in vivo.
abstract: OBJECTIVE
  Phenotypic switch of vascular smooth muscle cells (VSMCs) plays a key role in the pathogenesis of different vascular diseases, such as atherosclerosis and restenosis after coronary intervention. MicroRNAs have been identified as key regulators of VSMC biology. The miR-23b is highly expressed in VSMCs and it is involved in differentiation, proliferation, and migration of several non-vascular cell types. However, the role of miR-23b in vascular disease is currently unknown. Thus, the aim of the present study was to evaluate the role of miR-23b on VSMC phenotypic switch in vitro and after vascular injury in vivo.
  
  
  RESULTS
  To determine the changes of miR-23b expression in the injured arterial wall, we used the standard rat carotid artery balloon injury model. In vivo studies demonstrated that miR-23b is down-regulated after vascular injury. Gain-of-function studies showed that overexpression of miR-23b inhibited VSMC proliferation and migration, whereas the opposite effect was obtained with the in vitro inhibition of miR-23b. We further demonstrated that miR-23b can significantly promote the expression of VSMC marker genes such as smooth muscle α-actin (ACTA2) and smooth muscle myosin heavy chain (MYH11). Overexpression of miR-23b in balloon-injured arteries by Ad-miR-23b markedly decreased neointimal hyperplasia. Finally, miR-23b specifically suppresses urokinase-type plasminogen activator, SMAD family member 3, and transcription factor forkhead box O4 (FoxO4) expression in phenotypically modulated VSMCs. By luciferase reporter assay, we validated the transcription factor FoxO4 as a direct target of miR-23b in VSMCs.
  
  
  CONCLUSIONS
  We identify miR-23b as a novel regulator of VSMC phenotypic switch in vitro and following vascular injury in vivo.
authors.affiliation: Laboratory of Molecular and Cellular Cardiology, Cardiovascular Institute, Magna Graecia University, Catanzaro, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Iaconetti
authors.affiliation: Laboratory of Molecular and Cellular Cardiology, Cardiovascular Institute, Magna Graecia University, Catanzaro, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: De Rosa
authors.affiliation: Laboratory of Molecular and Cellular Cardiology, Cardiovascular Institute, Magna Graecia University, Catanzaro, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Polimeni
authors.affiliation: Laboratory of Molecular and Cellular Cardiology, Cardiovascular Institute, Magna Graecia University, Catanzaro, Italy.
authors.forename: Sabato
authors.initials: S
authors.lastname: Sorrentino
authors.affiliation: Laboratory of Molecular and Cellular Cardiology, Cardiovascular Institute, Magna Graecia University, Catanzaro, Italy.
authors.forename: Clarice
authors.initials: C
authors.lastname: Gareri
authors.affiliation: Laboratory of Molecular and Cellular Cardiology, Cardiovascular Institute, Magna Graecia University, Catanzaro, Italy.
authors.forename: Annarita
authors.initials: A
authors.lastname: Carino
authors.affiliation: Laboratory of Molecular and Cellular Cardiology, Cardiovascular Institute, Magna Graecia University, Catanzaro, Italy.
authors.forename: Jolanda
authors.initials: J
authors.lastname: Sabatino
authors.affiliation: Laboratory of Molecular and Cellular Cardiology, Cardiovascular Institute, Magna Graecia University, Catanzaro, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Colangelo
authors.affiliation: Laboratory of Molecular and Cellular Cardiology, Cardiovascular Institute, Magna Graecia University, Catanzaro, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Curcio
authors.affiliation: Laboratory of Molecular and Cellular Cardiology, Cardiovascular Institute, Magna Graecia University, Catanzaro, Italy URT-CNR, Magna Graecia University, Catanzaro 88100, Italy indolfi@unicz.it.
authors.forename: Ciro
authors.initials: C
authors.lastname: Indolfi
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics*; D049109:Cell Proliferation / Q000235:genetics*; D002478:Cells, Cultured; D015536:Down-Regulation; D035683:MicroRNAs / Q000235:genetics*; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000378:metabolism*; D010641:Phenotype; D051381:Rats
chemical_list: D035683:MicroRNAs; C000590974:MIRN23a microRNA, rat
keywords: FoxO4; MicroRNAs; Phenotypic switch; Restenosis; Vascular smooth muscle cells