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Erschienen in: Journal of Gastroenterology 7/2017

27.04.2017 | Review

Reflux esophagitis and its role in the pathogenesis of Barrett’s metaplasia

verfasst von: Rhonda Frances Souza

Erschienen in: Journal of Gastroenterology | Ausgabe 7/2017

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Abstract

Reflux esophagitis damages the squamous epithelium that normally lines the esophagus, and promotes replacement of the damaged squamous lining by the intestinal metaplasia of Barrett’s esophagus, the precursor of esophageal adenocarcinoma. Therefore, to prevent the development of Barrett’s metaplasia and esophageal adenocarcinoma, the pathogenesis of reflux esophagitis must be understood. We have reported that reflux esophagitis, both in a rat model and in humans, develops as a cytokine-mediated inflammatory injury (i.e., cytokine sizzle), not as a caustic chemical injury (i.e., acid burn), as traditionally has been assumed. Moreover, reflux induces activation of hypoxia inducible factor (HIF)-2α, which enhances the transcriptional activity of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) causing increases in pro-inflammatory cytokines and in migration of T lymphocytes, an underlying molecular mechanism for this cytokine-mediated injury. In some individuals, reflux esophagitis heals with Barrett’s metaplasia. A number of possibilities exist for the origin of the progenitor cells that give rise to this intestinal metaplasia including those of the esophagus, the proximal stomach, or the bone marrow. However, intestinal cells are not normally found in the esophagus, the stomach, or the bone marrow. Thus, the development of Barrett’s intestinal metaplasia must involve some molecular reprogramming of key developmental transcription factors within the progenitor cell, a process termed transcommitment, which may be initiated by the noxious components of the gastric refluxate. This review will highlight recent studies on the pathogenesis of reflux esophagitis and on reflux-related molecular reprogramming of esophageal squamous epithelial cells in the pathogenesis of Barrett’s metaplasia.
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Metadaten
Titel
Reflux esophagitis and its role in the pathogenesis of Barrett’s metaplasia
verfasst von
Rhonda Frances Souza
Publikationsdatum
27.04.2017
Verlag
Springer Japan
Erschienen in
Journal of Gastroenterology / Ausgabe 7/2017
Print ISSN: 0944-1174
Elektronische ISSN: 1435-5922
DOI
https://doi.org/10.1007/s00535-017-1342-1

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