Molecules involved in the development of Barrett’s esophagus phenotype in chronic eosinophilic esophagitis

Abstract

Objectives: Investigate the molecules involved in development of Barrett's esophagus (BE) in human EoE. Methods: Histopathological, immunohistochemical, real-time PCR and ELISA analyses are performed to identify the signature genes and proteins involved in the progression of BE in EoE. Results: We detected characteristic feature of BE like intermediate columnar type epithelial cells, induced BE signature genes like ErbB3, CDX1, ErbB2IP in the esophageal mucosa of EoE patients. In addition, we several BE associated diagnostic proteins TFF3, p53 and the progression marker like EGFR, p16, MICA, MICB and MHC molecules in esophageal biopsies of chronic EoE patients. Interestingly, we also detected mucin-producing columnar cells and MUC-2, MUC-4 and MUC5AC genes and proteins along with induced IL-9 in chronic EoE patients. A strong correlation of IL-9 with mucin genes are observed that implicated a possible role for IL-9 in the transformation of esophageal squamous epithelial cells to columnar epithelial cells in EoE patients. These findings indicates that IL-9 may has an important role in BE development in chronic EoE patients. Furthermore, our in vitro data of IL-9 exposure to primary esophageal epithelial cells provide evidence that IL-9 is involved in the induction mucins producing and epithelial barrier cells transcripts and proteins like CK8/18. GATA4, SOX9, TFF1, MUC5AC, including tight junction proteins. Conclusions: Taken together, these findings provide evidence that indeed IL-9 has a role in the initiation and progression of BE characteristics like development of mucin producing columnar epithelial cells in chronic EoE patients.