Bile Salts at Low pH Cause Dilation of Intercellular Spaces in In Vitro Stratified Primary Esophageal Cells, Possibly by Modulating Wnt Signaling.

Authors:
Dr. Sayak Ghatak, PhD, MBBS
Dr. Sayak Ghatak, PhD, MBBS
University of Rochester
Post-doctoral Associate
Esophagus
Rochester, NY | United States

J Gastrointest Surg 2016 Mar 29;20(3):500-9. Epub 2015 Dec 29.

University Hospitals Cleveland, Cleveland, OH, USA.

Background: The presence of dilated intercellular spaces in the stratified squamous lining of the esophagus is the pathognomonic feature of reflux esophagitis secondary to gastroesophageal reflux disease (GERD). In addition to stomach acid, bile salts are major constituents of gastroesophageal refluxate. The aim of our study was to determine the effect of bile salts cocktail at different pHs on epithelial junctions in an in vitro transwell model of stratified esophageal squamous epithelium.

Discussion: Human telomerase reverse transcriptase (hTERT) immortalized primary esophageal EPC1 cells were grown on polyester transwell surfaces in calcium-enriched media. The cells exhibited gradual stratification into an 11-layered squamous epithelium over 7 days, together with epithelial barrier function as indicated by increased transepithelial electrical resistance (TEER). This stratified epithelium demonstrated well-formed tight junctions, adherens junctions, and desmosomes as visualized by immunofluorescence and electron microscopy. When exposed to short pulses of bile salts at pH 5, but not either condition alone, there was loss of stratification and decrease in TEER, concomitant with disruption of adherens junctions, tight junctions, and desmosomes, leading to the appearance of dilated intercellular spaces. At the cellular level, bile salts at pH 5 activated the Wnt pathway (indicated by increased β-catenin Ser552 phosphorylation).

Conclusion: In conclusion, in our in vitro transwell model bile salts at pH 5, but not bile salts or media at pH 5 alone, modulate Wnt signaling, disrupt different junctional complexes, and cause increased permeability of stratified squamous esophageal epithelium. These changes approximate the appearance of dilated intercellular space similar to that found in GERD patients.

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http://dx.doi.org/10.1007/s11605-015-3062-2DOI Listing
March 2016
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References

(Supplied by CrossRef)
Article in Am J Gastroenterol
KR DeVault et al.
Am J Gastroenterol 2005
Article in Am J Physiol Gastrointest Liver Physiol
RF Souza et al.
Am J Physiol Gastrointest Liver Physiol 2008
Article in Surgery
WK Kauer et al.
Surgery 1997
Article in J Clin Invest
RC Orlando et al.
J Clin Invest 1981
Article in Gut
R Farre et al.
Gut 2008
Article in Pulm Pharmacol Ther
RC Orlando et al.
Pulm Pharmacol Ther 2011
Article in J Lipid Res
AF Hofmann et al.
J Lipid Res 1992
Article in Free Radic Biol Med
Y Araki et al.
Free Radic Biol Med 2005
Article in Biochem Biophys Res Commun
H Yasuda et al.
Biochem Biophys Res Commun 2007
Article in Journal of Gastrointestinal Surgery
S Ghatak et al.
Journal of Gastrointestinal Surgery 2013

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