Physiopathology of Esophageal Inflammation, Ulcerogenesis and Repair by Studying the Profile of Glycoconjugate

Esophageal inflammation is the highly complex protective response to cellular/tissue injury, one of the fundamental features in gastroesophageal reflux disease (GERD) that represents a wide group of acidrelated disorders, where a majority of patients appear to have nonerosive reflux disease (NERD) with minimal change esophagitis and no endoscopic abnormalities. Despite recent advances and better understanding of the physiopathogenesis of GERD and NERD, the molecular events of inflammation leading to erosive esophagitis (EE) and nonerosive esophagitis (NEE) development, their delay in healing and recurrence remains unclear. Membrane and integral glycoconjugate transformation of different cells in the esophageal barrier (EB) is associated with the reprogramming of pathways that control inflammation, survival and proliferation. The focus of this review is to summarize our data on the bidirectional relationship between the glycoconjugates – variable mediators for structural, modality roles and inflammatory settings in esophageal disorders. We designed and carried out experimental studies that induced esophageal damage, mimicking the esophageal injury of human GERD and NERD. We examined it using functional, morphologic and molecular biologic tests, and which and if pathways of inflammation precede changes in EB and development of mucosal lesions during the early stages of NEE or EE. We showed that glycoconjugates operate as tags for esophageal mucosal inflammation, ulceration and control communication between cell populations in repair. Detailed characterization of sialoglycans and their dynamics offers insights into functional interplay in the esophageal cellular community, whereas they switch the proinflammatory events involved in early nonepithelial cell activation and mucosal restitution. Esophageal mucosal repair and ulcer healing through different responses cannot be separated from changes in glycoconjugates upon modulation activity of limited and localized inflammation, cytotoxic nitrogen effects, and oxidative injury of epithelial and endothelial cells, cell proliferation, and migration. This new approach to glycobiology will provide an innovative view on inflammation in the physiopathogenesis of NERD and GERD. Copyright © 2012 S. Karger AG, Basel Esophageal barrier (EB) integrity, function and viability are critically dependent on the crosstalk of epithelial and stromal determinants implicated in counteraction to