ArticleGastroenterology2010
Aberrant epithelial-mesenchymal Hedgehog signaling characterizes Barrett's metaplasia.
Article in Gastroenterology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 101 papers.
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Who cites it
101 citing papers in PubMed, 183 citations in OpenAlex.
- Transcriptomic Profiling of Laser Capture Microdissected FFPE Esophageal Tissues Identifies Candidate Genes and Pathways Associated with Esophageal Adenocarcinoma.International journal of molecular sciences · 2026Article
- Targeting APE1-Redox Function Reverses SOX9-mediated Chemoresistance in Esophageal Adenocarcinoma.Gastroenterology · 2026Article
- Single-cell and bulk omics uncover fibroblast heterogeneity and HSPH1 as a key driver in Barrett's esophagus to esophageal adenocarcinoma progression.Cancer cell international · 2026Article
- Intrinsic mechanisms and microenvironmental cues fine-tune plasticity of esophageal progenitors.Nature communications · 2026Article
- Epithelial architecture and signaling activity in the adult human esophagus.Frontiers in cell and developmental biology · 2025Review
- The role of the fibroblast in Barrett's esophagus and esophageal adenocarcinoma.Current opinion in gastroenterology · 2024Review
- Impact of TRP Channels on Extracellular Matrix Remodeling: Focus on TRPV4 and Collagen.International journal of molecular sciences · 2024Review
- Transcriptomic Insights into Hub Genes, Immune Infiltration, and Candidate Drugs in Erosive Esophagitis.Journal of inflammation research · 2024Article
- Modelling esophageal adenocarcinoma and Barrett's esophagus with patient-derived organoids.Frontiers in molecular biosciences · 2024Review
- Ligand-dependent hedgehog signaling maintains an undifferentiated, malignant osteosarcoma phenotype.Oncogene · 2023Article
- Translating Molecular Biology Discoveries to Develop Targeted Cancer Interception in Barrett's Esophagus.International journal of molecular sciences · 2023Review
- Signaling Pathways in the Pathogenesis of Barrett's Esophagus and Esophageal Adenocarcinoma.International journal of molecular sciences · 2023Review
- Cancer Risk in Barrett's Esophagus: A Clinical Review.International journal of molecular sciences · 2023Review
- The role of bile acid in intestinal metaplasia.Frontiers in physiology · 2023Review
- Hybrid argon plasma coagulation in Barrett's esophagus: a systematic review and meta-analysis.Clinical endoscopy · 2023Article
- Hedgehog signaling mechanism and role in cancer.Seminars in cancer biology · 2022Review
- Inflammatory and Proliferative Pathway Activation in Human Esophageal Myofibroblasts Treated with Acidic Bile Salts.International journal of molecular sciences · 2022Article
- Mechanisms and pathophysiology of Barrett oesophagus.Nature reviews. Gastroenterology & hepatology · 2022Review
- Selective targeting BMP2 and 4 in SMAD4 negative esophageal adenocarcinoma inhibits tumor growth and aggressiveness in preclinical models.Cellular oncology (Dordrecht, Netherlands) · 2022Article
- A human Barrett's esophagus organoid system reveals epithelial-mesenchymal plasticity induced by acid and bile salts.American journal of physiology. Gastrointestinal and liver physiology · 2022Article
41 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
15 authors at 7 institutions in 3 countries.
Funding
Abstract
BACKGROUND &
aimsThe molecular mechanism underlying epithelial metaplasia in Barrett's esophagus remains unknown. Recognizing that Hedgehog signaling is required for early esophageal development, we sought to determine if the Hedgehog pathway is reactivated in Barrett's esophagus, and if genes downstream of the pathway could promote columnar differentiation of esophageal epithelium.
methodsImmunohistochemistry, immunofluorescence, and quantitative real-time polymerase chain reaction were used to analyze clinical specimens, human esophageal cell lines, and mouse esophagi. Human esophageal squamous epithelial (HET-1A) and adenocarcinoma (OE33) cells were subjected to acid treatment and used in transfection experiments. Swiss Webster mice were used in a surgical model of bile reflux injury. An in vivo transplant culture system was created using esophageal epithelium from Sonic hedgehog transgenic mice.
resultsMarked up-regulation of Hedgehog ligand expression, which can be induced by acid or bile exposure, occurs frequently in Barrett's epithelium and is associated with stromal expression of the Hedgehog target genes PTCH1 and BMP4. BMP4 signaling induces expression of SOX9, an intestinal crypt transcription factor, which is highly expressed in Barrett's epithelium. We further show that expression of Deleted in Malignant Brain Tumors 1, the human homologue of the columnar cell factor Hensin, occurs in Barrett's epithelium and is induced by SOX9. Finally, transgenic expression of Sonic hedgehog in mouse esophageal epithelium induces expression of stromal Bmp4, epithelial Sox9, and columnar cytokeratins.
conclusionsEpithelial Hedgehog ligand expression may contribute to the initiation of Barrett's esophagus through induction of stromal BMP4, which triggers reprogramming of esophageal epithelium in favor of a columnar phenotype.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.