title: Down-regulation of mir-542-3p promotes neointimal formation in the aging rat.
abstract: OBJECTIVE
  To explore mir-542-3p mediated inhibition of vascular smooth muscle cell (VSMC) proliferation through the inhibition of Syk activation.
  
  
  RESULTS
  MicroRNA (mir)-542-3p was selected for analysis based on miRNA microarray and qRT-PCR results. In vitro mir-542-3p expression was significantly downregulated in old (o)VSMCs compared with young (y)VSMCs under serum stimulation conditions. Upregulation of mir-542-3p in oVSMCs significantly inhibited VSMC proliferation, whereas downregulation of mir-542-3p in yVSMCs increased VSMC proliferation. We identified spleen tyrosine kinase (Syk) as a direct target of mir-542-3p by database search, and showed that its expression and phosphorylation were higher in oVSMCs than in yVSMCs after serum stimulation. Luciferase assays confirmed that Syk is a direct target of miR-3542-3p. Knock-down of mir-542-3p in yVSMCs inhibited the activation of the Syk downstream effectors STAT3 and STAT5, whereas mir-542-3p overexpression enhanced STAT3 and STAT5 activities. In a rat balloon injury model, mir-542-3p inhibited neointima formation and proliferating cell nuclear antigen (PCNA) protein expression.
  
  
  CONCLUSIONS
  Mir-542-3p modulates VSMC proliferation via the Syk/STAT3-STAT5 axis. Downregulation of mir-542-3p may explain age-related neointimal hyperplasia in rats.
authors.affiliation: Department of Cardiology, Second hospital affiliated to Third military medical university, XinQiao Hospital, ChongQing, 400037, China.
authors.forename: De-hui
authors.initials: DH
authors.lastname: Qian
authors.affiliation: Department of Geriatrics, First hospital affiliated to Third military medical university, Southwest Hospital, ChongQing, 400038, China.
authors.forename: Pan
authors.initials: P
authors.lastname: Gao
authors.affiliation: Division of Nursing, Second hospital affiliated to Third military medical university, XinQiao Hospital, ChongQing, 400037, China.
authors.forename: Huan
authors.initials: H
authors.lastname: Feng
authors.affiliation: Department of Cardiology, Second hospital affiliated to Third military medical university, XinQiao Hospital, ChongQing, 400037, China.
authors.forename: Zhe-Xue
authors.initials: ZX
authors.lastname: Qin
authors.affiliation: Department of Cardiology, Second hospital affiliated to Third military medical university, XinQiao Hospital, ChongQing, 400037, China.
authors.forename: Jia-bei
authors.initials: JB
authors.lastname: Li
authors.affiliation: Department of Cardiology, Second hospital affiliated to Third military medical university, XinQiao Hospital, ChongQing, 400037, China. Electronic address: Huanglan260@126.com.
authors.forename: Lan
authors.initials: L
authors.lastname: Huang
mesh_terms: D000375:Aging / Q000235:genetics*; D000818:Animals; D049109:Cell Proliferation / Q000235:genetics; D015536:Down-Regulation / Q000235:genetics*; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000378:metabolism; D058426:Neointima / Q000235:genetics*; D010766:Phosphorylation / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000235:genetics; D015854:Up-Regulation
chemical_list: D035683:MicroRNAs
keywords: Aging; MicroRNA; Proliferation; Syk; Vascular smooth muscle cells