title: MicroRNA-133 controls vascular smooth muscle cell phenotypic switch in vitro and vascular remodeling in vivo.
abstract: BACKGROUND
  MicroRNA (miR)-1 and -133 play a crucial role in skeletal and cardiac muscle biology and pathophysiology. However, their expression and regulation in vascular cell physiology and disease is currently unknown.
  
  
  OBJECTIVE
  The aim of the present study was to evaluate the role, if any, of miR-1 and miR-133 in vascular smooth muscle cell (VSMC) phenotypic switch in vitro and in vivo.
  
  
  RESULTS
  We demonstrate here that miR-133 is robustly expressed in vascular smooth muscle cells (VSMCs) in vitro and in vivo, whereas miR-1 vascular levels are negligible. miR-133 has a potent inhibitory role on VSMC phenotypic switch in vitro and in vivo, whereas miR-1 does not have any relevant effect per se. miR-133 expression is regulated by extracellular signal-regulated kinase 1/2 activation and is inversely correlated with VSMC growth. Indeed, miR-133 decreases when VSMCs are primed to proliferate in vitro and following vascular injury in vivo, whereas it increases when VSMCs are coaxed back to quiescence in vitro and in vivo. miR-133 loss- and gain-of-function experiments show that miR-133 plays a mechanistic role in VSMC growth. Accordingly, adeno-miR-133 reduces but anti-miR-133 exacerbates VSMC proliferation and migration in vitro and in vivo. miR-133 specifically suppresses the transcription factor Sp-1 expression in vitro and in vivo and through Sp-1 repression regulates smooth muscle gene expression.
  
  
  CONCLUSIONS
  Our data show that miR-133 is a key regulator of vascular smooth muscle cell phenotypic switch in vitro and in vivo, suggesting its potential therapeutic application for vascular diseases.
authors.affiliation: Cardiovascular Institute, Laboratory of Molecular and Cellular Cardiology, Department of Experimental and Clinical Medicine, Magna Graecia University, Germaneto, Catanzaro, Italy. dtorella@unicz.it
authors.forename: Daniele
authors.initials: D
authors.lastname: Torella
authors.forename: Claudio
authors.initials: C
authors.lastname: Iaconetti
authors.forename: Daniele
authors.initials: D
authors.lastname: Catalucci
authors.forename: Georgina M
authors.initials: GM
authors.lastname: Ellison
authors.forename: Angelo
authors.initials: A
authors.lastname: Leone
authors.forename: Cheryl D
authors.initials: CD
authors.lastname: Waring
authors.forename: Angela
authors.initials: A
authors.lastname: Bochicchio
authors.forename: Carla
authors.initials: C
authors.lastname: Vicinanza
authors.forename: Iolanda
authors.initials: I
authors.lastname: Aquila
authors.forename: Antonio
authors.initials: A
authors.lastname: Curcio
authors.forename: Gianluigi
authors.initials: G
authors.lastname: Condorelli
authors.forename: Ciro
authors.initials: C
authors.lastname: Indolfi
mesh_terms: D000818:Animals; D020212:Carotid Artery Injuries / Q000235:genetics / Q000473:pathology; D049109:Cell Proliferation; D008297:Male; D035683:MicroRNAs / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000473:pathology* / Q000502:physiology*; D032389:Myocytes, Smooth Muscle / Q000473:pathology* / Q000502:physiology*; D010641:Phenotype; D051381:Rats; D017208:Rats, Wistar
chemical_list: C549446:MIRN133 microRNA, rat; D035683:MicroRNAs