The incidence of eosinophilic esophagitis has increased in the past several years, yet our understanding of pathogenesis remains limited. To test the hypothesis that microRNAs are altered in children with eosinophilic esophagitis, microRNAs were profiled in esophageal mucosa biopsies obtained from patients with active disease (n=5) and healthy control subjects (n=6). Fourteen microRNAs were significantly altered between groups, four of which were decreased in eosinophilic esophagitis patients. A panel of five microRNAs (miR-203, miR-375, miR-21, miR-223, and miR-142-3p) was selected for validation in an independent set of control (n=22), active disease (n=22), inactive disease (n=22), and gastroesphogeal reflux disease patient samples (n=6). Each panel microRNA was significantly altered among groups. MicroRNA changes observed in esophageal biopsies were not reflected in the circulating RNA pool, as no differences in panel microRNA levels were observed in sera collected from the four patient groups. In addition, no change in esophageal microRNA levels was detected following treatment that resolved esophageal eosinophilia, a result in contrast to previous studies. In an effort to identify the ramifications of reduced esophageal miR-203, miR-203 activity was inhibited in cultured epithelial cells via expression of a tough decoy miRNA inhibitor. Luciferase reporter assays demonstrated that miR-203 does not directly regulate human IL-15 through targeting of the IL-15 3'UTR. From these experiments, it is concluded that microRNAs are perturbed in the esophageal mucosa, but not the serum, of pediatric eosinophilic esophagitis patients. Further investigation is required to decipher pathologically relevant consequences of microRNA perturbation in this context.
- eosinophilic esophagitis
- Copyright © 2014, American Journal of Physiology- Gastrointestinal and Liver Physiology