Down-regulation of a morphogen (sonic hedgehog) gradient in the gastric epithelium of Helicobacter pylori-infected Mongolian gerbils

Hidekazu Suzuki, Yuriko Minegishi, Yohei Nomoto, Takayuki Ota, Tatsuhiro Masaoka, Gijs R. van den Brink, Toshifumi Hibi

Research output: Contribution to journalArticlepeer-review

68 Citations (Scopus)


Sonic hedgehog (Shh) is a morphogen involved in many aspects of patterning of the gut during embryogenesis and in gastric fundic gland homeostasis in the adult. Intestinal metaplastic change of the gastric epithelium is associated with the loss of Shh expression, and mice that lack Shh expression show intestinal transformation of the gastric mucosa. The present study was designed to investigate the alteration of Shh expression in the stomach of an experimental model of Helicobacter pylori (H. pylori) colonization. Male Mongolian gerbils were inoculated with H. pylori and examined 4 and 51 weeks later. The level of Shh mRNA expression was determined by quantitative RT-PCR and in situ hybridization. Shh protein expression was determined by immunoblotting and immunohistochemistry. Shh was expressed in the parietal cells, zymogenic cells, and mucous neck cells of the gastric fundic glands of gerbils. Prolonged colonization by H. pylori led to extension of the inflammation from the antrum to the corpus of the stomach, with loss of Shh expression. Loss of Shh expression correlated with loss of parietal cells, disturbed maturation of the mucous neck cell-zymogenic cell lineage, and increased cellular proliferation. Shh expression is significantly reduced in H. pylori-associated gastritis. These data show for the first time that H. pylori infection leads to down-regulation of the expression of a morphogen with an established role (Shh) in gastric epithelial differentiation.

Original languageEnglish
Pages (from-to)186-197
Number of pages12
JournalJournal of Pathology
Issue number2
Publication statusPublished - 2005 Jun
Externally publishedYes


  • Atrophy
  • Gastritis
  • Helicobacter pylori
  • Mongolian gerbils
  • Parietal cell
  • Sonic hedgehog
  • Zymogenic cell

ASJC Scopus subject areas

  • Pathology and Forensic Medicine


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