Columnar-Lined Esophagus Develops via Wound Repair in a Surgical Model of Reflux Esophagitis

Agoston T. Agoston, Thai H. Pham, Robert D. Odze, David H. Wang, Kiron M. Das, Stuart J. Spechler, Rhonda F. Souza

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Background & Aims: After esophagojejunostomy, rodents develop reflux esophagitis and a columnar-lined esophagus with features of Barrett's metaplasia. This rodent columnar-lined esophagus has been proposed to develop from cellular reprogramming of progenitor cells, but studies on early columnar-lined esophagus development are lacking. We performed a systematic, histologic, and immunophenotypic analysis of columnar-lined esophagus development in rats after esophagojejunostomy. Methods: At various times after esophagojejunostomy in 52 rats, the esophagus was removed and tissue sections were evaluated for type, location, and length of columnar lining. Molecular characteristics were evaluated by immunohistochemistry and immunofluorescence. Results: At week 2, ulceration was seen in esophageal squamous epithelium, starting distally at the esophagojejunostomy anastomosis. Re-epithelialization of the distal ulcer segment occurred via proliferation and expansion of immature-appearing glands budding directly off jejunal crypts, characteristic of wound healing. The columnar-lined esophagus's immunoprofile was similar to jejunal crypt epithelium, and columnar-lined esophagus length increased significantly from 0.15 mm (±0.1 SEM) at 2 weeks to 5.22 mm (±0.37) at 32 weeks. Neoglands were found within esophageal ulcer beds, and spindle-shaped cells expressing epithelial-mesenchymal transition markers were found at the columnar-lined esophagus's leading edge. Only proliferative squamous epithelium was found at the proximal ulcer border. Conclusions: After esophagojejunostomy in rats, metaplastic columnar-lined esophagus develops via a wound healing process that does not appear to involve cellular reprogramming of progenitor cells. This process involves EMT-associated migration of jejunal cells into the esophagus, where they likely have a competitive advantage over squamous cells in the setting of ongoing gastroesophageal reflux disease.

Original languageEnglish (US)
Pages (from-to)389-404
Number of pages16
JournalCMGH
Volume6
Issue number4
DOIs
StatePublished - Jan 1 2018

Fingerprint

Anatomic Models
Peptic Esophagitis
Esophagus
Wounds and Injuries
Ulcer
Epithelium
Wound Healing
Rodentia
Stem Cells
Re-Epithelialization
Epithelial-Mesenchymal Transition
Barrett Esophagus
Gastroesophageal Reflux
Cell Movement
Fluorescent Antibody Technique
Epithelial Cells
Immunohistochemistry

Keywords

  • Barrett's Esophagus
  • Epithelial-Mesenchymal Transition
  • Gastroesophageal Reflux

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

Cite this

Columnar-Lined Esophagus Develops via Wound Repair in a Surgical Model of Reflux Esophagitis. / Agoston, Agoston T.; Pham, Thai H.; Odze, Robert D.; Wang, David H.; Das, Kiron M.; Spechler, Stuart J.; Souza, Rhonda F.

In: CMGH, Vol. 6, No. 4, 01.01.2018, p. 389-404.

Research output: Contribution to journalArticle

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AU - Pham, Thai H.

AU - Odze, Robert D.

AU - Wang, David H.

AU - Das, Kiron M.

AU - Spechler, Stuart J.

AU - Souza, Rhonda F.

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AB - Background & Aims: After esophagojejunostomy, rodents develop reflux esophagitis and a columnar-lined esophagus with features of Barrett's metaplasia. This rodent columnar-lined esophagus has been proposed to develop from cellular reprogramming of progenitor cells, but studies on early columnar-lined esophagus development are lacking. We performed a systematic, histologic, and immunophenotypic analysis of columnar-lined esophagus development in rats after esophagojejunostomy. Methods: At various times after esophagojejunostomy in 52 rats, the esophagus was removed and tissue sections were evaluated for type, location, and length of columnar lining. Molecular characteristics were evaluated by immunohistochemistry and immunofluorescence. Results: At week 2, ulceration was seen in esophageal squamous epithelium, starting distally at the esophagojejunostomy anastomosis. Re-epithelialization of the distal ulcer segment occurred via proliferation and expansion of immature-appearing glands budding directly off jejunal crypts, characteristic of wound healing. The columnar-lined esophagus's immunoprofile was similar to jejunal crypt epithelium, and columnar-lined esophagus length increased significantly from 0.15 mm (±0.1 SEM) at 2 weeks to 5.22 mm (±0.37) at 32 weeks. Neoglands were found within esophageal ulcer beds, and spindle-shaped cells expressing epithelial-mesenchymal transition markers were found at the columnar-lined esophagus's leading edge. Only proliferative squamous epithelium was found at the proximal ulcer border. Conclusions: After esophagojejunostomy in rats, metaplastic columnar-lined esophagus develops via a wound healing process that does not appear to involve cellular reprogramming of progenitor cells. This process involves EMT-associated migration of jejunal cells into the esophagus, where they likely have a competitive advantage over squamous cells in the setting of ongoing gastroesophageal reflux disease.

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