{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T09:09:43Z","timestamp":1790068183937,"version":"4.0.1"},"reference-count":36,"publisher":"BMJ","issue":"7","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Gut"],"published-print":{"date-parts":[[2007,7]]},"abstract":"<jats:p>\n                  <jats:bold>Background:<\/jats:bold> Retinoic acid (RA) is a powerful differentiation agent. Barrett\u2019s oesophagus occurs when duodeno-gastro-oesophageal reflux causes squamous epithelium (SE) tissue to become columnar epithelium tissue by an unknown mechanism. The bile acid lithocholic acid (LCA) competes for the retinoid X receptor retinoid binding site. Hence, RA pathways may be implicated in Barrett\u2019s oesophagus.<\/jats:p>\n               <jats:p>\n                  <jats:bold>Methods:<\/jats:bold> RA activity in tissues and cell lines treated with all<jats:italic>-trans<\/jats:italic> retinoic acid (ATRA) with or without LCA was assessed using a reporter. Expression of p21 was determined by real-time PCR in Barrett\u2019s oesophagus cell lines with or without LCA. SE and Barrett\u2019s oesophagus biopsy specimens were exposed to 100 \u03bcM of ATRA or 20 mM of a RA inhibitor, citral, in organ culture for &gt;72 h. Characteristics of treated specimens, compared with untreated controls, were analysed by immunohistochemical analysis (cytokeratins (CKs), vimentin) and RT-PCR (CKs). Confocal microscopy assessed temporal changes in co-localisation of CK8\/18 and vimentin. Cell proliferation was assessed by bromo-deoxyuridine incorporation and immunohistochemical analysis for Ki67 and p21.<\/jats:p>\n               <jats:p>\n                  <jats:bold>Results:<\/jats:bold> RA biosynthesis was increased in Barrett\u2019s oesophagus compared with SE (p&lt;0.001). LCA and ATRA caused a synergistic increase in RA signalling as shown by increased p21 (p&lt;0.01). Morphological and molecular analysis of SE exposed to ATRA showed columnar differentiation independent of proliferation. Metaplasia could be induced from the stromal compartment alone and vimentin expression co-localised with CK8\/18 at 24 h, which separated into CK8\/18-positive glands and vimentin-positive stroma by 48 h. Citral-treated Barrett\u2019s oesophagus led to phenotypic and immunohistochemical characteristics of SE, which was independent of proliferation.<\/jats:p>\n               <jats:p>\n                  <jats:bold>Conclusion:<\/jats:bold> RA activity is increased in Barrett\u2019s oesophagus and is induced by LCA. Under conditions of altered RA activity and an intact stroma, the oesophageal phenotype can be altered independent of proliferation.<\/jats:p>","DOI":"10.1136\/gut.2006.097915","type":"journal-article","created":{"date-parts":[[2006,12,21]],"date-time":"2006-12-21T20:29:03Z","timestamp":1166732943000},"page":"906-917","source":"Crossref","is-referenced-by-count":52,"title":["Retinoic acid-induced glandular differentiation of the oesophagus"],"prefix":"10.1136","volume":"56","author":[{"given":"Chih-Long","family":"Chang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre","family":"Lao-Sirieix","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vicki","family":"Save","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guillermo","family":"De La Cueva 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