title: The microRNA miR-132 targets Lrrfip1 to block vascular smooth muscle cell proliferation and neointimal hyperplasia.
abstract: OBJECTIVE
  The proliferation and remodeling of vascular smooth muscle cells (VSMCs) is an important pathological event in atherosclerosis and restenosis. Here we report that microRNA-132 (miR-132) blocks vascular smooth muscle cells (VSMC) proliferation by inhibiting the expression of LRRFIP1 [leucine-rich repeat (in Flightless 1) interacting protein-1].
  
  
  RESULTS
  MicroRNA microarray revealed that miR-132 was upregulated in the rat carotid artery after catheter injury, which was further confirmed by quantitative real-time RT-PCR. Transfection of a miR-132 mimic significantly inhibited the proliferation of VSMCs, whereas transfection of a miR-132 antagomir increased it. miR-132 mimic inhibited VSMC migration and induced apoptosis. miR-132 mimic increased the protein amounts of both p27 and smooth muscle (SM) α-actin, whereas it decreased SM α-actin and Bcl2. Bioinformatics showed that LRRFIP1 is a target candidate of miR-132. miR-132 down-regulated luciferase activity driven by a vector containing the 3'-untranslated region of Lrrfip1 in a sequence-specific manner. LRRFIP1 induced VSMC proliferation and increased phosphorylation of ERK. Immunohistochemical analysis revealed that Lrrfip1 was clearly expressed along with the basal laminar area of smooth muscle, and its expression pattern was disrupted 7 days after arterial injury. LRRFIP1 mRNA was decreased 14 days after injury. Delivery of miR-132 to rat carotid artery reduced LRRFIP1 expression and attenuated neointimal proliferation in carotid artery injury models.
  
  
  CONCLUSIONS
  Our results suggest that miR-132 is a novel regulator of VSMC proliferation that represses neointimal formation by inhibiting LRRFIP1 expression.
authors.affiliation: Department of Pharmacology, Medical Research Center for Gene Regulation, and National Research Laboratory for Heart and Muscle Diseases, Chonnam National University Medical School, Gwangju 501-746, Republic of Korea.
authors.forename: Nakwon
authors.initials: N
authors.lastname: Choe
authors.forename: Jin-Sook
authors.initials: JS
authors.lastname: Kwon
authors.forename: Ju-Ryoung
authors.initials: JR
authors.lastname: Kim
authors.forename: Gwang Hyeon
authors.initials: GH
authors.lastname: Eom
authors.forename: Yongsook
authors.initials: Y
authors.lastname: Kim
authors.forename: Kwang-Il
authors.initials: KI
authors.lastname: Nam
authors.forename: Youngkeun
authors.initials: Y
authors.lastname: Ahn
authors.forename: Hae Jin
authors.initials: HJ
authors.lastname: Kee
authors.forename: Hyun
authors.initials: H
authors.lastname: Kook
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D050197:Atherosclerosis / Q000378:metabolism* / Q000473:pathology; D001483:Base Sequence; D002404:Catheterization / Q000009:adverse effects; D002454:Cell Differentiation / Q000502:physiology; D002460:Cell Line; D049109:Cell Proliferation; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism; D004195:Disease Models, Animal; D006965:Hyperplasia / Q000378:metabolism / Q000473:pathology; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D058426:Neointima / Q000378:metabolism* / Q000473:pathology; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000199:Actins; C493962:Cdkn1b protein, rat; C583985:LRRFIP1 protein, rat; C548821:MIRN132 microRNA, rat; D035683:MicroRNAs; D016601:RNA-Binding Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27
keywords: Atherosclerosis; Leucine-rich repeat (in flightless 1) interacting protein-1; Neointimal hyperplasia; Vascular smooth muscle cells; miR-132