Expression of Sonic hedgehog (SHH) and CDX2 in the columnar epithelium of the lower oesophagus.
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.
Yamanaka
Yoshiyuki
Y
Department of Internal Medicine, Kawasaki Medical School, Japan. yamanaka@med.kawasaki-m.ac.jp
Shiotani
Akiko
A
Fujimura
Yoshinori
Y
Ishii
Manabu
M
Fujita
Minoru
M
Matsumoto
Hiroshi
H
Tarumi
Ken-ichi
K
Kamada
Tomoari
T
Hata
Jiro
J
Haruma
Ken
K
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
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