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

Research output: Contribution to journalReview article

10 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)767-776
Number of pages10
JournalJournal of Gastroenterology
Volume52
Issue number7
DOIs
StatePublished - Jul 1 2017

Fingerprint

Peptic Esophagitis
Barrett Esophagus
Cytokines
Esophagus
Stomach
Metaplasia
Wounds and Injuries
Adenocarcinoma
Stem Cells
Bone Marrow
Caustics
B-Lymphocytes
Transcription Factors
Epithelium
Epithelial Cells
T-Lymphocytes
Light
Acids

Keywords

  • Barrett’s esophagus
  • Cdx2
  • Cytokine
  • NF-κB
  • Squamous cells

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Reflux esophagitis and its role in the pathogenesis of Barrett’s metaplasia. / Souza, Rhonda Frances.

In: Journal of Gastroenterology, Vol. 52, No. 7, 01.07.2017, p. 767-776.

Research output: Contribution to journalReview article

@article{fb1b45b7ab6244e3b98ce8721ba7dd7e,
title = "Reflux esophagitis and its role in the pathogenesis of Barrett’s metaplasia",
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.",
keywords = "Barrett’s esophagus, Cdx2, Cytokine, NF-κB, Squamous cells",
author = "Souza, {Rhonda Frances}",
year = "2017",
month = "7",
day = "1",
doi = "10.1007/s00535-017-1342-1",
language = "English (US)",
volume = "52",
pages = "767--776",
journal = "Journal of Gastroenterology",
issn = "0944-1174",
publisher = "Springer Japan",
number = "7",

}

TY - JOUR

T1 - Reflux esophagitis and its role in the pathogenesis of Barrett’s metaplasia

AU - Souza, Rhonda Frances

PY - 2017/7/1

Y1 - 2017/7/1

N2 - 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.

AB - 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.

KW - Barrett’s esophagus

KW - Cdx2

KW - Cytokine

KW - NF-κB

KW - Squamous cells

UR - http://www.scopus.com/inward/record.url?scp=85018273326&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85018273326&partnerID=8YFLogxK

U2 - 10.1007/s00535-017-1342-1

DO - 10.1007/s00535-017-1342-1

M3 - Review article

C2 - 28451845

AN - SCOPUS:85018273326

VL - 52

SP - 767

EP - 776

JO - Journal of Gastroenterology

JF - Journal of Gastroenterology

SN - 0944-1174

IS - 7

ER -