The Effect of Retinoic Acid and Deoxycholic Acid on the Differentiation of Primary Human Esophageal Keratinocytes
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The mechanism linking gastroduodenal reflux disease to intestinal metaplasia in the esophagus (Barrett’s esophagus) has not been determined. Active conjugate metabolites of retinoic acid, in addition to bile acids, undergo an enterohepatic circulation in bile. Retinoic acid and bile acids are candidate mediators of keratinocyte transdifferentiation in Barrett’s esophagus. We studied the effects of retinoic acid on the differentiation of primary human esophageal keratinocytes cultured in vitro. Retinoic acid induces expression of a marker of intestinal differentiation, MUC2, in these cells. However, retinoic acid, alone or in combination with the hydrophobic bile acid, deoxycholic acid, does not affect esophageal keratinocyte squamous differentiation as assessed by involucrin expression and cellular morphology. The ability of retinoic acid to induce MUC2 expression may be relevant to the pathogenesis of Barrett’s esophagus. However, this does not result in suppression of squamous differentiation.
KeywordsRetinoic acid Barrett’s esophagus Metaplasia Bile acids
We thank Dr. Hugh Mulcahy for help in recruiting patients for this study and Dr. Fiona Watt and Mr. Simon Broad, CRUK, for help with the supply of several reagents. Dr. Gordon Cooke was supported by a grant from the Irish Lung Foundation.
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