title: Emergence of spasmolytic polypeptide-expressing metaplasia in Mongolian gerbils infected with Helicobacter pylori.
abstract: Spasmolytic polypeptide (TFF2)-expressing metaplasia (SPEM) is observed in mucosa adjacent to human gastric cancer and in fundic glands showing oxyntic atrophy in Helicobacter felis-infected mice. Mongolian gerbils infected with Helicobacter pylori (Hp) develop goblet cell intestinal metaplasia and adenocarcinoma, but the presence of SPEM has not been studied in gerbils. We therefore have sought to examine the development of metaplastic mucosal changes in Hp-infected Mongolian gerbils. Mongolian gerbils were assigned to either uninfected controls or infected with Hp at 17 weeks of age. The animals were killed at 17, 20, 26, 31, 41 and 56 weeks of age. Stomach sections were stained using antibodies for TFF2, intrinsic factor, H/K-ATPase, BrdU and MUC2. Dual immunofluorescence staining for TFF2 with intrinsic factor and for TFF2 with MUC2 was performed. In uninfected animals, no SPEM or intestinal metaplasia was observed. Infected gerbils developed SPEM initially in the intermediate zone along the lesser curvature and subsequently spread out towards the greater curvature. In the earlier stages of infection, SPEM glands demonstrated TFF2 and intrinsic factor double staining cells. However, after 35 weeks of infection, the number of double staining SPEM cells decreased. While early in infection SPEM organized in straight glands, in the later stages of infections, SPEM glands became distorted or dilated along with the development of gastritis cystica profunda that was TFF2 positive. Goblet cell intestinal metaplasia developed only late in the infection. Dual staining for TFF2 and MUC2 showed glands containing both SPEM- and MUC2-positive goblet cell intestinal metaplasia. SPEM develops early in Hp infection in Mongolian gerbils, and alterations in gland morphology arise from SPEM glands during the course of gastric infection with goblet cell intestinal metaplasia developing subsequent to SPEM.
authors.affiliation: Department of Gastrointestinal Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Nao
authors.initials: N
authors.lastname: Yoshizawa
authors.forename: Yoshiharu
authors.initials: Y
authors.lastname: Takenaka
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Yamaguchi
authors.forename: Tsukamoto
authors.initials: T
authors.lastname: Tetsuya
authors.forename: Harunari
authors.initials: H
authors.lastname: Tanaka
authors.forename: Masae
authors.initials: M
authors.lastname: Tatematsu
authors.forename: Sachiyo
authors.initials: S
authors.lastname: Nomura
authors.forename: James R
authors.initials: JR
authors.lastname: Goldenring
authors.forename: Michio
authors.initials: M
authors.lastname: Kaminishi
mesh_terms: D000818:Animals; D005753:Gastric Mucosa / Q000378:metabolism / Q000473:pathology; D005849:Gerbillinae; D020397:Goblet Cells / Q000378:metabolism / Q000473:pathology; D016481:Helicobacter Infections / Q000378:metabolism / Q000473:pathology*; D016480:Helicobacter pylori; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D008679:Metaplasia; D010455:Peptides / Q000378:metabolism*; D013270:Stomach / Q000473:pathology*; D000071164:Trefoil Factor-2
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; C000604007:TFF2 protein, human; D000071164:Trefoil Factor-2; C451060:spasmolytic polypeptide