title: Expression of Sonic hedgehog (SHH) and CDX2 in the columnar epithelium of the lower oesophagus.
abstract: BACKGROUND
  Decreases in Sonic hedgehog (SHH) and CDX2 expression are associated with atrophy and intestinal metaplasia in the gastric mucosa. The pathogenesis of development of Barrett's oesophagus is still unclear.
  
  
  OBJECTIVE
  To examine the gene expression of CDX2 and SHH and their signalling pathways in the columnar epithelium and the association with endoscopic appearance, gastric pH or bile acids.
  
  
  METHODS
  Sixty-three patients with metaplastic columnar epithelium of the lower oesophagus were studied. Whole biopsy specimens and microdissected tissues were examined for messenger RNA.
  
  
  RESULTS
  BMP4 expression was significantly higher in patients with tubular mucosal patterns of columnar epithelium visualised by Narrow Band Imaging with magnification. The expression of SHH was significantly lower and that of CDX2 was higher in the goblet columnar epithelium than in non-goblet columnar epithelium. CDX2 expression was significantly higher in the patients with hypoacidity than in the others. BMP4 and PTCH1 expression was significantly higher in the group with higher concentrations of deoxycholic acid than in the group with lower concentrations.
  
  
  CONCLUSIONS
  SHH might be the initial factor inducing columnar metaplasia, and subsequent or simultaneous BMP4 stimuli might induce the CDX2 expression that causes goblet-cell metaplasia.
authors.affiliation: Department of Internal Medicine, Kawasaki Medical School, Japan. yamanaka@med.kawasaki-m.ac.jp
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Yamanaka
authors.forename: Akiko
authors.initials: A
authors.lastname: Shiotani
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Fujimura
authors.forename: Manabu
authors.initials: M
authors.lastname: Ishii
authors.forename: Minoru
authors.initials: M
authors.lastname: Fujita
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Matsumoto
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Tarumi
authors.forename: Tomoari
authors.initials: T
authors.lastname: Kamada
authors.forename: Jiro
authors.initials: J
authors.lastname: Hata
authors.forename: Ken
authors.initials: K
authors.lastname: Haruma
mesh_terms: D000368:Aged; D001471:Barrett Esophagus / Q000235:genetics / Q000473:pathology; D015415:Biomarkers; D055415:Bone Morphogenetic Protein 4 / Q000378:metabolism; D000071616:CDX2 Transcription Factor; D003840:Deoxycholic Acid / Q000032:analysis; D004847:Epithelial Cells / Q000378:metabolism*; D004947:Esophagus / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005750:Gastric Juice / Q000737:chemistry; D015870:Gene Expression; D053823:Hedgehog Proteins / Q000235:genetics* / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008297:Male; D008875:Middle Aged; D055271:Mucin 5AC / Q000378:metabolism; D055272:Mucin-6 / Q000378:metabolism; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D011956:Receptors, Cell Surface / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics
chemical_list: C525809:BMP4 protein, human; D015415:Biomarkers; D055415:Bone Morphogenetic Protein 4; D000071616:CDX2 Transcription Factor; C491270:CDX2 protein, human; D053823:Hedgehog Proteins; D018398:Homeodomain Proteins; C524678:MUC5AC protein, human; C524734:MUC6 protein, human; D055271:Mucin 5AC; D055272:Mucin-6; C000606236:PTCH1 protein, human; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D011956:Receptors, Cell Surface; D003840:Deoxycholic Acid