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01-06-2009

Validation of a rodent model of Barrett’s esophagus using quantitative gene expression profiling

Authors: Daniel S. Oh, Steven R. DeMeester, Christy M. Dunst, Ryutaro Mori, Bethany J. Lehman, Hidekazu Kuramochi, Kathleen Danenberg, Peter Danenberg, Jeffrey A. Hagen, Parakrama Chandrasoma, Tom R. DeMeester

Published in: Surgical Endoscopy | Issue 6/2009

Abstract

Background

A rodent model of gastroduodenal–esophageal reflux can result in replacement of squamous esophageal mucosa with intestinal-type columnar mucosa and carcinoma. The validity of this model is debated, as it is unproven whether this mucosa is intestinal metaplasia due to reflux or represents migration of adjacent jejunal mucosa above the anastomosis. The aim of this study was to evaluate the esophageal intestinal-type mucosa in these animals by measuring expression of trefoil factor genes (TFF-1, -2, -3) and comparing it with adjacent jejunum in order to determine its etiology.

Methods

Twenty-five rats underwent esophagojejunostomy at the ligament of Treitz to induce reflux of gastric and duodenal contents. The animals were sacrificed at 16 weeks (n = 14) and 30 weeks (n = 11). After sacrifice, the distal esophagus, jejunum, and colon were obtained. RNA was isolated, reverse transcribed, and messenger RNA (mRNA) expression of TFF-1, -2, and -3 was measured with real-time polymerase chain reaction (PCR). Linear discriminant analysis classified samples based on gene expression.

Results

Esophageal intestinal-type mucosa was present at sacrifice in 18 animals. Compared to jejunum, the expression of TFF-1 and TFF-2 mRNA in the intestinal mucosa of the distal esophagus was increased (p = 0.0007 and p < 0.0001, respectively). Expression of TFF-3 was also increased in esophageal intestinal mucosa compared with jejunum (p = 0.0002), but there was significant overlap in expression between these tissues for this gene. Linear discriminant analysis misclassified esophageal intestinal-type mucosa as jejunum in only one case. In no cases was jejunum misclassified as esophageal intestinal-type mucosa.

Conclusion

The gene expression profile of esophageal intestinal-type mucosa following surgically induced reflux in a rodent model indicates that this represents intestinal metaplasia, not proximal migration of jejunum. This validates this model for studying the pathogenesis of Barrett’s esophagus. Use of this model has potential for assessment of the impact of various therapies on the natural history of reflux disease.

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Title: Validation of a rodent model of Barrett’s esophagus using quantitative gene expression profiling
Authors: Daniel S. Oh
Steven R. DeMeester
Christy M. Dunst
Ryutaro Mori
Bethany J. Lehman
Hidekazu Kuramochi
Kathleen Danenberg
Peter Danenberg
Jeffrey A. Hagen
Parakrama Chandrasoma
Tom R. DeMeester
Publication date: 01-06-2009
Publisher: Springer-Verlag
Published in: Surgical Endoscopy / Issue 6/2009
Print ISSN: 0930-2794
Electronic ISSN: 1432-2218
DOI: https://doi.org/10.1007/s00464-008-0169-5

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Validation of a rodent model of Barrett’s esophagus using quantitative gene expression profiling

Abstract

Background

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

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