title: Characterization of progressive metaplasia in the gastric corpus mucosa of Mongolian gerbils infected with Helicobacter pylori.
abstract: Spasmolytic polypeptide-expressing metaplasia (SPEM) and intestinal metaplasia are considered neoplastic precursors of gastric adenocarcinoma in humans. Loss of parietal cells causes the development of SPEM in the gastric corpus and then chronic inflammation drives SPEM toward a more proliferative lineage. Mongolian gerbils infected with Helicobacter pylori develop chronic gastritis and metaplasia, mimicking aspects of human gastritis with H. pylori infection. We therefore examined metaplastic lineages in the gastric corpus mucosa of gerbils infected by H. pylori strain 7.13, which produces rapid onset of severe inflammation. Six weeks following H. pylori infection, Griffonia simplicifolia lectin II (GSII)-positive SPEM developed in the base of oxyntic glands in association with parietal cell loss and inflammation. In association with severe inflammation, SPEM glands evolved into aberrant phenotypes, including branched lesions, dilated lesions, and penetrating invasive glands. Mucin 4 (MUC4) was up-regulated in SPEM and progressive SPEM. Clusterin was expressed in the tips of branched and dilated lesions and throughout regions of invasive glands. Intriguingly, clusterin-positive regions in these lesions expressed Ki67 and matrix metalloproteinase 7 (MMP-7). These same regions were also positive for expression of phospho-IkBα, suggestive of activated NFkB signalling. These findings suggest that clusterin-positive regions in progressive phenotypes of SPEM have invasive characteristics. Thus, H. pylori infection in gerbils induces SPEM, which then can progress to further aberrant and invasive metaplastic phenotypes. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
authors.affiliation: Nashville VA Medical Center, Nashville, Tennessee, USA.|Departments of Surgery and Cell and Developmental Biology and the Epithelial Biology Center, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Shimizu
authors.affiliation: Nashville VA Medical Center, Nashville, Tennessee, USA.|Departments of Surgery and Cell and Developmental Biology and the Epithelial Biology Center, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
authors.forename: Eunyoung
authors.initials: E
authors.lastname: Choi
authors.affiliation: Nashville VA Medical Center, Nashville, Tennessee, USA.|Departments of Surgery and Cell and Developmental Biology and the Epithelial Biology Center, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
authors.forename: Christine P
authors.initials: CP
authors.lastname: Petersen
authors.affiliation: Division of Gastroenterology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Noto
authors.affiliation: Division of Gastroenterology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
authors.forename: Judith
authors.initials: J
authors.lastname: Romero-Gallo
authors.affiliation: Division of Gastroenterology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
authors.forename: Maria B
authors.initials: MB
authors.lastname: Piazuelo
authors.affiliation: Department of Pathology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
authors.forename: M Kay
authors.initials: MK
authors.lastname: Washington
authors.affiliation: Division of Gastroenterology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.|Department of Cancer Biology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
authors.forename: Richard M
authors.initials: RM
authors.lastname: Peek
authors.affiliation: Nashville VA Medical Center, Nashville, Tennessee, USA.|Departments of Surgery and Cell and Developmental Biology and the Epithelial Biology Center, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
authors.forename: James R
authors.initials: JR
authors.lastname: Goldenring
mesh_terms: D000818:Animals; D051152:Clusterin / Q000378:metabolism; D005753:Gastric Mucosa / Q000378:metabolism / Q000382:microbiology / Q000473:pathology*; D005849:Gerbillinae; D016481:Helicobacter Infections / Q000150:complications / Q000382:microbiology / Q000473:pathology*; D016480:Helicobacter pylori; D007249:Inflammation / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D008297:Male; D008679:Metaplasia / Q000209:etiology / Q000382:microbiology / Q000473:pathology; D055264:Mucin-4 / Q000378:metabolism
chemical_list: D051152:Clusterin; D055264:Mucin-4
keywords: GSII; IkBα; MMP-7; MUC4; SPEM; clusterin; gastritis; intestinal metaplasia