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.
- 5.Baltes S, Nau H, Lampen A (2004) All-trans retinoic acid enhances differentiation and influences permeability of intestinal Caco-2 cells under serum-free conditions. Dev Growth Differ 46:503–514. doi: 10.1111/j.1440-169x.2004.00765.x
- 7.Zimber A, Chedeville A, Abita JP, Barbu V, Gespach C (2000) Functional interactions between bile acids, all-trans retinoic acid, and 1,25-Dihydroxy-vitamin D3 on monocytic differentiation and myeloblastin gene down-regulation in HL60 and THP-1 human leukaemia cells. Cancer Res 60:672–678PubMedGoogle Scholar
- 10.Chang CL, Lao-Sirieix P, Save V, De La Cueva Mendez G, Laskey R, Fitzgerald RC (2007) Retinoic acid-induced glandular differentiation of the esophagus. Gut 56:906–917. doi: 10.1136/gut.2006.097915
- 13.Watt FM (1998) Cultivation of human epidermal keratinocytes with a 3T3 feeder layer. In: Celis JE (ed) Cell biology: a laboratory handbook, vol 1. Academic Press, New York, pp 113–118Google Scholar
- 14.Chantret I, Rodolosse A, Barbat A, Dussaulx E, Brot-Laroche E, Zweibaum A, Rousset M (1994) Differential expression of sucrase-isomaltase in clones isolated from early and late passages of the cell line Caco2: evidence for glucose-dependent negative regulation. J Cell Sci 107:213–225PubMedGoogle Scholar
- 15.Ishiquro K, Sartorelli AC (2004) Activation of transiently transfected reporter genes in 3T3 Swiss cells by the inducers of differentiation/apoptosis-dimethylsulfoxide, hexamethylene bisacetamide and trichostatin A. Eur J Biochem 271:2379–2390. doi: 10.1111/j.1432-1033.2004.04157.x
- 17.Watt FM (1994) Suspension-induced terminal differentiation of keratinocytes. In: Leigh IM, Watt FM (eds) Keratinocyte methods. Cambridge University Press, Cambridge, UK, pp 113Google Scholar
- 18.Watt FM, Jordan PW, O’Neill C (1988) Cell shape controls terminal differentiation of human epidermal keratinocytes. Proc Natl Acad Sci USA 85:5576–5580. doi: 10.1073/pnas.85.15.5576
- 19.Murphy GF, Flynn TC, Rice RH, Pinkus GS (1984) Involucrin expression in normal and neoplastic human skin: a marker for keratinocyte differentiation. J Invest Dermatol 82:453–457. doi: 10.1111/1523-1747.ep12260945