Fundic mucosal change associated with oxyntic atrophy

Hirokazu Yamaguchi, Jeffrey R Lee, James R. Goldenring, Michio Kaminishi

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

The normal gastric fundic mucosa is assembled from a diverse group of cell lineages responsible for lumenal secretion of mucins, pepsinogen, intrinsic factor, and HCl. A number of investigations over the past decade have demonstrated that lineages in the normal fundic mucosa arise from a progenitor zone located in the glands [1]. In the gastric mucosa, the progenitor zone is located at two-thirds of the mucosa from the base, and this location is maintained by the differentiation of cell lineages with differing longevity. Short-lived surface mucous cells having a 4-to 6-day lifetime arise from the progenitor zone and migrate toward the lumen [2]. Although a minority of parietal cells migrate toward the luminal surface, the majority of parietal cells migrate toward the basal lamina [3]. Mucous neck cells arise from preneck cells, and it is thought that they redifferentiate into chief cells during migration toward the base [4]. Those cells have a long lifetime, such as 80 days in parietal cells and 200 days in chief cells. This process of differentiation of specific cell lineages from the progenitor zone is regulated by hormonal and paracrine regulators. To maintain mucosal integrity, the gastric mucosa responds to both mechanical and caustic injuries. Chronic injury by Helicobacter pylori infection leads to oxyntic atrophy, foveolar hyperplasia, and mucous cell metaplasia [5,6]. Recent investigations have described TFF2/spasmolytic polypeptide expressing metaplasia (SPEM) in mice infected with Helicobacter felis [7], in humans with fundal predominant H. pylori gastritis [8], and in the mucosa adjacent to gastric adenocarcinoma [8-10]. The cells of this lineage recapitulate the morphology of duodenal Brunner's glands or the cells of the deep antral glands and immunostain for the trefoil polypeptide spasmolytic polypeptide (SP), also known as TFF2. SPEM was identified in a high percentage of gastric fundic biopsies with H. pylori gastritis, and within the adjacent mucosa in 91% of gastric cancer resections. In addition, most of these sections demonstrated SP staining cells within dysplastic cells [8]. The association of SPEM with gastric adenocarcinoma and oxyntic atrophy suggested that SPEM may represent a candidate precursor to gastric adenocarcinoma. In addition to its association with Helicobacter gastritis, SPEM is also observed in other animal models with oxyntic atrophy. Metallothionein-tumor necrosis factor (TGF)-a transgenic mice demonstrate not only expansion of the surface cell compartment of fundic glands but also marked decrease of parietal cells and emergence of SPEM at the base of fundic glands [11,12]. Another model is rats administrated with DMP-777 that leads to a reversible pharmacological ablation of parietal cells [13]. This drug is a cell permeant neutrophil elastase inhibitor that also acts as a parietal cell-specific protonophore. Treatment of rats with DMP-777 for 3 months induced oxyntic atrophy and expansion of the surface compartment as well as the emergence of SPEM from the base of fundic glands [13]. These results support the hypothesis that loss of parietal cells may be a primary event in evolution of the spectrum of lineage changes. Furthermore, the production of SPEM the base of fundic mucosa suggested the presence of a second cryptic progenitor zone at the base of the glands. Previous gastric resection is a risk factor for the development of gastric remnant cancer [14]. Causative factors have been investigated, including duodenogastric bile reflux, intragastric bacterial flora overgrowth with an increase in carcinogenic Nnitroso compounds, denervation, and decreased vascularity [15]. Remnant stomachs show oxyntic atrophy, and remnant gastric cancer develops in the fundic glands; therefore, remnant gastric cancer is another good model for investigating the association between SPEM, oxyntic atrophy, and gastric cancer development.

Original languageEnglish (US)
Title of host publicationThe Diversity of Gastric Carcinoma
Subtitle of host publicationPathogenesis, Diagnosis, and Therapy
PublisherSpringer Tokyo
Pages87-96
Number of pages10
ISBN (Print)443121139X, 9784431211396
DOIs
StatePublished - Dec 1 2005

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Atrophy
Metaplasia
Gastric Stump
Stomach Neoplasms
DMP 777
Cell Lineage
Stomach
Mucous Membrane
Gastritis
Gastric Mucosa
Helicobacter pylori
Adenocarcinoma
Helicobacter felis
spasmolytic polypeptide
Secretory Proteinase Inhibitory Proteins
Brunner Glands
Bile Reflux
Duodenogastric Reflux
Helicobacter
Pepsinogen A

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Yamaguchi, H., Lee, J. R., Goldenring, J. R., & Kaminishi, M. (2005). Fundic mucosal change associated with oxyntic atrophy. In The Diversity of Gastric Carcinoma: Pathogenesis, Diagnosis, and Therapy (pp. 87-96). Springer Tokyo. https://doi.org/10.1007/4-431-27713-7_5

Fundic mucosal change associated with oxyntic atrophy. / Yamaguchi, Hirokazu; Lee, Jeffrey R; Goldenring, James R.; Kaminishi, Michio.

The Diversity of Gastric Carcinoma: Pathogenesis, Diagnosis, and Therapy. Springer Tokyo, 2005. p. 87-96.

Research output: Chapter in Book/Report/Conference proceedingChapter

Yamaguchi, H, Lee, JR, Goldenring, JR & Kaminishi, M 2005, Fundic mucosal change associated with oxyntic atrophy. in The Diversity of Gastric Carcinoma: Pathogenesis, Diagnosis, and Therapy. Springer Tokyo, pp. 87-96. https://doi.org/10.1007/4-431-27713-7_5
Yamaguchi H, Lee JR, Goldenring JR, Kaminishi M. Fundic mucosal change associated with oxyntic atrophy. In The Diversity of Gastric Carcinoma: Pathogenesis, Diagnosis, and Therapy. Springer Tokyo. 2005. p. 87-96 https://doi.org/10.1007/4-431-27713-7_5
Yamaguchi, Hirokazu ; Lee, Jeffrey R ; Goldenring, James R. ; Kaminishi, Michio. / Fundic mucosal change associated with oxyntic atrophy. The Diversity of Gastric Carcinoma: Pathogenesis, Diagnosis, and Therapy. Springer Tokyo, 2005. pp. 87-96
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