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

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. Conclusion 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.