ArticleGut2006
Bile acids directly augment caudal related homeobox gene Cdx2 expression in oesophageal keratinocytes in Barrett's epithelium.
Article in Gut, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 97 papers.
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Who cites it
97 citing papers in PubMed, 181 citations in OpenAlex.
- A TRIM15-CDX2 loop drives bile acid-induced gastric intestinal metaplasia.Molecular medicine (Cambridge, Mass.) · 2026Article
- How to Define the Gastroesophageal Junction.Digestive endoscopy : official journal of the Japan Gastroenterological Endoscopy Society · 2026Review
- Weiyan Tongluo Granules attenuate gastric intestinal metaplasia through PPARγ/NF-κB/CDX2 signaling pathway.Chinese medicine · 2026Article
- FOLR2Journal of experimental & clinical cancer research : CR · 2024Article
- Development of a novel oncolytic adenovirus controlled by CDX2 promoter for esophageal adenocarcinoma therapy.Journal of gastroenterology · 2024Article
- Distinctive duodenal microbiomes and bile acid profiles in duodenal tumor patients revealed by prospective observational study.Scientific reports · 2024Observational
- Gastro-Esophageal Junction Precancerosis: Histological Diagnostic Approach and Pathogenetic Insights.Cancers · 2023Review
- Review
- Signaling Pathways in the Pathogenesis of Barrett's Esophagus and Esophageal Adenocarcinoma.International journal of molecular sciences · 2023Review
- The role of bile acid in intestinal metaplasia.Frontiers in physiology · 2023Review
- Pluripotency of periodontal ligament and dental pulp cells is induced by intercellular communication via the CDX2/Oct-4/Sox2 pathway.Annals of translational medicine · 2022Article
- Article
- Mechanism of Bile Acid-Induced Programmed Cell Death and Drug Discovery against Cancer: A Review.International journal of molecular sciences · 2022Review
- Iron deficiency linked to altered bile acid metabolism promotes Helicobacter pylori-induced inflammation-driven gastric carcinogenesis.The Journal of clinical investigation · 2022Article
- Analysis of Barrett's Esophagus and Its Risk Factors: A Cross-Sectional Study of 10,122 Subjects at a Japanese Health Examination Center.Digestion · 2022Article
- Expression and significance of CDX2, FXR, and TGR5 in esophageal cancer.International journal of clinical and experimental pathology · 2022Article
- HDAC6/FOXP3/HNF4α axis promotes bile acids induced gastric intestinal metaplasia.American journal of cancer research · 2022Article
- Article
- Molecular biomarker identification for esophageal adenocarcinoma using endoscopic brushing and magnified endoscopy.Esophagus : official journal of the Japan Esophageal Society · 2021Article
- Epithelial cell transforming 2 is regulated by Yes-associated protein 1 and mediates pancreatic cancer progression and metastasis.American journal of physiology. Gastrointestinal and liver physiology · 2021Article
37 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND AND
aimsThe mechanism of transformation to intestinal metaplasia in Barrett's oesophagus has not been clarified. We investigated the effects of various bile acids on expression of the caudal related homeobox gene Cdx2 in cultured oesophageal squamous epithelial cells. In addition, morphological and histochemical changes in squamous cells to intestinal epithelial cells were studied in response to bile acid induced expression of Cdx2.
methodsA rat model of Barrett's oesophagus was created by anastomosing the oesophagus and jejunum, and Cdx2 expression was investigated by immunohistochemistry. Also, the response of various bile acids on Cdx2 gene expression was studied in the human colon epithelial cell lines Caco-2 and HT-29, as well as in cultured rat oesophageal squamous epithelial cells using a Cdx2 promoter luciferase assay. In addition, primary cultured oesophageal squamous epithelial cells were transfected with Cdx2 expression vectors and their possible transformation to intestinal-type epithelial cells was investigated.
resultsOesophagojejunal anastomoses formed intestinal goblet cell metaplasia in rat oesophagus specimens and metaplastic epithelia strongly expressed Cdx2. When the effects of 11 types of bile acids on Cdx2 gene expression were examined, only cholic acid (CA) and dehydrocholic acid dose dependently increased Cdx2 promoter activity and Cdx2 protein production in Caco-2 and HT-29 cells, and cultured rat oesophageal keratinocytes. Results from mutation analysis of Cdx2 promoter suggested that two nuclear factor kappaB (NFkappaB) binding sites were responsible for the bile acid induced activation of the Cdx2 promoter. When bile acids were measured in oesophageal refluxate of rats with experimental Barrett's oesophagus, the concentration of CA was found to be consistent with the experimental dose that augmented Cdx2 expression in vitro. Furthermore, transfection of the Cdx2 expression vector in cultured rat oesophageal keratinocytes induced production of intestinal-type mucin, MUC2, in cells that expressed Cdx2.
conclusionsWe found that CA activates Cdx2 promoter via NFkappaB and stimulates production of Cdx2 protein in oesophageal keratinocytes with production of intestinal-type mucin. This may be one of the mechanisms of metaplasia in Barrett's oesophagus.
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