title: MicroRNA-15b/16 Attenuates Vascular Neointima Formation by Promoting the Contractile Phenotype of Vascular Smooth Muscle Through Targeting YAP.
abstract: OBJECTIVE
  To investigate the functional role of the microRNA (miR)-15b/16 in vascular smooth muscle (SM) phenotypic modulation.
  
  
  RESULTS
  We found that miR-15b/16 is one of the most abundant mRs expressed in contractile vascular smooth muscle cells (VSMCs). However, when contractile VSMCs get converted to a synthetic phenotype, miR-15b/16 expression is significantly reduced. Knocking down endogenous miR-15b/16 in VSMCs attenuates SM-specific gene expression but promotes VSMC proliferation and migration. Conversely, overexpression of miR-15b/16 promotes SM contractile gene expression while attenuating VSMC migration and proliferation. Consistent with this, overexpression of miR-15b/16 in a rat carotid balloon injury model markedly attenuates injury-induced SM dedifferentiation and neointima formation. Mechanistically, we identified the potent oncoprotein yes-associated protein (YAP) as a downstream target of miR-15b/16 in VSMCs. Reporter assays validated that miR-15b/16 targets YAP's 3' untranslated region. Moreover, overexpression of miR-15b/16 significantly represses YAP expression, whereas conversely, depletion of endogenous miR-15b/16 results in upregulation of YAP expression.
  
  
  CONCLUSIONS
  These results indicate that miR-15b/16 plays a critical role in SM phenotypic modulation at least partly through targeting YAP. Restoring expression of miR-15b/16 would be a potential therapeutic approach for treatment of proliferative vascular diseases.
authors: From the Department of Respiratory Medicine, The First Affiliated Hospital of Nanchang University, Nanchang, China (F.X., X.K., W.Z.); and Department of Pharmacology and Toxicology, Medical College of Georgia, Georgia Regents University, Augusta (A.S.I.A., X.K., G.H., F.L., J.Z.).
authors: Fei
authors: F
authors: Xu
authors: From the Department of Respiratory Medicine, The First Affiliated Hospital of Nanchang University, Nanchang, China (F.X., X.K., W.Z.); and Department of Pharmacology and Toxicology, Medical College of Georgia, Georgia Regents University, Augusta (A.S.I.A., X.K., G.H., F.L., J.Z.).
authors: Abu Shufian Ishtiaq
authors: AS
authors: Ahmed
authors: From the Department of Respiratory Medicine, The First Affiliated Hospital of Nanchang University, Nanchang, China (F.X., X.K., W.Z.); and Department of Pharmacology and Toxicology, Medical College of Georgia, Georgia Regents University, Augusta (A.S.I.A., X.K., G.H., F.L., J.Z.).
authors: Xiuhua
authors: X
authors: Kang
authors: From the Department of Respiratory Medicine, The First Affiliated Hospital of Nanchang University, Nanchang, China (F.X., X.K., W.Z.); and Department of Pharmacology and Toxicology, Medical College of Georgia, Georgia Regents University, Augusta (A.S.I.A., X.K., G.H., F.L., J.Z.).
authors: Guoqing
authors: G
authors: Hu
authors: From the Department of Respiratory Medicine, The First Affiliated Hospital of Nanchang University, Nanchang, China (F.X., X.K., W.Z.); and Department of Pharmacology and Toxicology, Medical College of Georgia, Georgia Regents University, Augusta (A.S.I.A., X.K., G.H., F.L., J.Z.).
authors: Fang
authors: F
authors: Liu
authors: From the Department of Respiratory Medicine, The First Affiliated Hospital of Nanchang University, Nanchang, China (F.X., X.K., W.Z.); and Department of Pharmacology and Toxicology, Medical College of Georgia, Georgia Regents University, Augusta (A.S.I.A., X.K., G.H., F.L., J.Z.).
authors: Wei
authors: W
authors: Zhang
authors: From the Department of Respiratory Medicine, The First Affiliated Hospital of Nanchang University, Nanchang, China (F.X., X.K., W.Z.); and Department of Pharmacology and Toxicology, Medical College of Georgia, Georgia Regents University, Augusta (A.S.I.A., X.K., G.H., F.L., J.Z.). jizhou@gru.edu.
authors: Jiliang
authors: J
authors: Zhou
mesh_terms: D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D020212:Carotid Artery Injuries / Q000378:metabolism / Q000503:physiopathology; D002465:Cell Movement / Q000235:genetics / Q000502:physiology; D049109:Cell Proliferation / Q000235:genetics; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D035683:MicroRNAs / Q000235:genetics*; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D058426:Neointima / Q000235:genetics* / Q000503:physiopathology; D010641:Phenotype; D051381:Rats; D012680:Sensitivity and Specificity; D000091102:YAP-Signaling Proteins
chemical_list: D051017:Apoptosis Regulatory Proteins; C547573:MIRN16 microRNA, rat; D035683:MicroRNAs; D000091102:YAP-Signaling Proteins; C509425:Yap1 protein, rat; C534110:mirn15 microRNA, rat
keywords: YAP; microRNA; neointima formation; phenotypic modulation; smooth muscle