title: miR-18a-5p MicroRNA Increases Vascular Smooth Muscle Cell Differentiation by Downregulating Syndecan4.
abstract: OBJECTIVE
  Differentiation and de-differentiation of vascular smooth muscle cells (VSMCs) are important events in atherosclerosis and restenosis after angioplasty. MicroRNAs are considered a key regulator in cellular processes such as differentiation, proliferation, and apoptosis. Here, we report the role of new miR-18a-5p microRNA and its downstream target genes in VSMCs and in a carotid balloon injury model.
  
  
  METHODS
  Expression of miR-18a-5p and its candidate genes was examined in VSMCs and in a carotid artery injury model by quantitative reverse-transcription polymerase chain reaction (qRT-PCR) and microRNA microarray analysis. VSMC differentiation marker genes including smooth muscle (SM) α-actin and SM22α were determined by Western blot, qRT-PCR, and a SM22α promoter study. Gene overexpression or knockdown was performed in VSMCs.
  
  
  RESULTS
  miR-18a-5p was upregulated in the rat carotid artery at the early time after balloon injury. Transfection of the miR-18a-5p mimic promoted the VSMC differentiation markers SM α-actin and SM22α. In addition, miR-18a-5p expression was induced in differentiated VSMCs, whereas it decreased in de-differentiated VSMCs. We identified syndecan4 as a downstream target of miR-18-5p in VSMCs. Overexpression of syndecan4 decreased Smad2 expression, whereas knockdown of syndecan4 increased Smad2 expression in VSMCs. Finally, we showed that Smad2 induced the expression of VSMC differentiation marker genes in VSMCs.
  
  
  CONCLUSIONS
  These results indicate that miR-18a-5p is involved in VSMC differentiation by targeting syndecan4.
authors.affiliation: Heart Research Center of Chonnam National University Hospital, Gwangju, Korea.
authors.forename: Hae Jin
authors.initials: HJ
authors.lastname: Kee
authors.affiliation: Heart Research Center of Chonnam National University Hospital, Gwangju, Korea.
authors.forename: Gwi Ran
authors.initials: GR
authors.lastname: Kim
authors.affiliation: Heart Research Center of Chonnam National University Hospital, Gwangju, Korea.
authors.forename: Soo-Na
authors.initials: SN
authors.lastname: Cho
authors.affiliation: Division of Cardiovascular and Rare Diseases, Center for Biomedical Sciences, Korea National Institute of Health, Cheongju, Korea.
authors.forename: Jin-Sook
authors.initials: JS
authors.lastname: Kwon
authors.affiliation: Heart Research Center of Chonnam National University Hospital, Gwangju, Korea.
authors.forename: Youngkeun
authors.initials: Y
authors.lastname: Ahn
authors.affiliation: Department of Pharmacology and Medical Research Center for Gene Regulation, Chonnam National University Medical School, Gwangju, Korea.
authors.forename: Hyun
authors.initials: H
authors.lastname: Kook
authors.affiliation: Heart Research Center of Chonnam National University Hospital, Gwangju, Korea.
authors.forename: Myung Ho
authors.initials: MH
authors.lastname: Jeong
keywords: Cell differentiation; Smad2 protein; Syndecan4; Vascular smooth muscle; miR-8a
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