title: Increased expression of vascular cell adhesion molecule 1 in muscle biopsy samples from juvenile dermatomyositis patients with short duration of untreated disease is regulated by miR-126.
abstract: OBJECTIVE
  To evaluate the effect of duration of untreated disease on vascular cell adhesion molecule 1 (VCAM-1) and microRNA (miRNA) expression in muscle biopsy samples from children with juvenile dermatomyositis (DM) as well as its effect on soluble VCAM-1 (sVCAM-1) and tumor necrosis factor α (TNFα) concentrations in sera from these children.
  
  
  METHODS
  We enrolled 28 untreated children with juvenile DM and 8 pediatric controls. Eleven children with juvenile DM had short duration of untreated disease (symptoms for ≤2 months before muscle biopsy), and 17 had long duration of untreated disease (symptoms for >2 months before muscle biopsy). Vascular structures, characterized by immunofluorescence using antibodies against von Willebrand factor, VCAM-1, and α-smooth muscle actin, were measured for total area and intensity. Circulating sVCAM-1 and TNFα levels were determined in patients with short duration of untreated disease, patients with long duration of untreated disease, and controls. Differential expression of microRNA-126 (miR-126) in muscle biopsy samples from the 2 patient groups and the control group was detected by miRNA expression profiling and confirmed by quantitative reverse transcription-polymerase chain reaction in muscle biopsy samples from the 3 groups.
  
  
  RESULTS
  Juvenile DM patients with short duration of untreated disease had significantly higher total positive area and intensity/high power field of VCAM-1 expression than did juvenile DM patients with long duration of untreated disease (P = 0.043 and P = 0.015, respectively) or controls (P = 0.004 and P = 0.001, respectively). Von Willebrand factor antigen-positive vasculature displayed greater VCAM-1 intensity in patients with short duration of untreated disease than in patients with long duration of untreated disease (P = 0.001). Circulating levels of sVCAM-1 and TNFα were significantly higher in patients with short duration of untreated disease than in controls (P = 0.013 and P = 0.048, respectively). The miRNA miR-126, a negative regulator of VCAM-1 expression, was significantly decreased (3.39-fold; P < 0.006) in patients with short duration of untreated disease compared to controls, while miR-126 expression in patients with long duration of untreated disease did not differ significantly compared to controls.
  
  
  CONCLUSIONS
  In patients with short duration of untreated disease, miR-126 down-regulation is associated with increased VCAM-1 in both muscle and blood, suggesting that VCAM-1 plays a critical role early in juvenile DM disease pathophysiology, augmented by TNFα.
authors: Children's Hospital of Chicago Research Center, Chicago, Illinois, USA.
authors: Erin
authors: E
authors: Kim
authors: Joan
authors: J
authors: Cook-Mills
authors: Gabrielle
authors: G
authors: Morgan
authors: Simone T
authors: ST
authors: Sredni
authors: Lauren M
authors: LM
authors: Pachman
mesh_terms: D001706:Biopsy; D002648:Child; D002675:Child, Preschool; D003882:Dermatomyositis / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D005260:Female; D006801:Humans; D053583:Interleukin-1beta / Q000097:blood / Q000276:immunology; D015850:Interleukin-6 / Q000097:blood / Q000276:immunology; D008297:Male; D035683:MicroRNAs / Q000502:physiology*; D018482:Muscle, Skeletal / Q000276:immunology* / Q000473:pathology; D059467:Transcriptome / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000276:immunology; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood / Q000235:genetics* / Q000276:immunology
chemical_list: C508600:IL6 protein, human; D053583:Interleukin-1beta; D015850:Interleukin-6; C527111:MIRN126 microRNA, human; D035683:MicroRNAs; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1