Early Helicobacter pylori eradication restores sonic hedgehog expression in the gastric mucosa of mongolian gerbils

Background and Aim: Sonic hedgehog (Shh) is a morphogen involved in the homeostasis of the gastric fundic glands. Alterations of gastric mucosal Shh expression after eradication of Helicobacter pylori were examined. Method: Mongolian gerbils were inoculated with H. pylori at the age of 5 weeks. H. pylori eradication was then carried out at 12, 24 or 48 weeks after the inoculation, and the gerbils were examined at 10 weeks after the eradication. Gastric inflammation was evaluated by the tissue myeloperoxidase activity and the histological scoring. Immunohistochemistry and in situ hybridization were performed for determining the Shh expression. Results: Significant decrease of the myeloperoxidase activity and scores for acute and chronic inflammation as well as atrophy were observed in the H. pylori-eradicated gerbils as compared with the findings in the non-H. pylori-eradicated gerbils. Significant increase of the horizontal length of the area positive for Shh expression was noted in the H. pylori-eradicated gerbils as compared with that in the non-H. pylori-eradicated gerbils. Earlier eradication promoted better restoration of Shh expression. 50% of the animals of the 24-week eradication group and all animals in the 48-week eradication group exhibited heterotopic proliferative glands. In the animals showing heterotopic proliferative glands, the front line of Shh regeneration was cut off at the point of development of heterotopic proliferative glands. Conclusion:H. pylori-associated deregulation of Shh expression that could be linked to gastric atrophy and the associated preneoplastic transformation appears to be reversible with early H. pylori eradication.