A molecular profile of the mouse gastric parietal cell with and without exposure to
            <i>Helicobacter pylori</i>

Mills, Jason C.; Syder, Andrew J.; Hong, Chieu V.; Guruge, Janaki L.; Raaii, Farhang; Gordon, Jeffrey I.

doi:10.1073/pnas.231332398

Cited by 77 publications

(62 citation statements)

References 39 publications

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“…We have recently used GeneChips and qRT-PCR to show that Hp1 colonization of GF mice has no demonstrable effect on the expression profile of parietal cells (42). The present study raises the question of what effects parietal cells and acid have on bacterial gene expression, and what bacterial genes are critical for entry into and persistence within host niches that are relatively devoid of acid.…”

Section: Discussionmentioning

confidence: 76%

The impact of parietal cells onHelicobacter pyloritropism and host pathology: An analysis using gnotobiotic normal and transgenic mice

Syder

Guruge

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

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Helicobacter pylori infection of the human stomach is common and typically benign, although a subset of hosts develops severe pathology. Infection occurs in an organ with distinct microenvironments characterized by pronounced differences in the composition of acid-producing parietal cells. In this study, we examine determinants of bacterial tropism to various gastric niches by using germ-free normal and transgenic mice with an engineered parietal cell ablation. Mice were colonized for 8 weeks with a clinical isolate (Hp1) that expresses adhesins recognized by epithelial NeuAc␣2,3Gal␤1,4 glycan receptors. In normal mice, Hp1 has tropism for a parietal cell-deficient niche where sialylated glycans are expressed by a narrow band of pit cells positioned at the boundary between the squamous epithelium (forestomach) and the proximal glandular epithelium. Lymphoid aggregates that develop in this niche, but not elsewhere in the stomach, were analyzed by GeneChip and quantitative RT-PCR studies of laser capture microdissected mucosa and yielded a series of biomarkers indicative of immune cell activation and maturation. Genetic ablation of parietal cells produced a new source of NeuAc␣2,3Gal␤1,4 glycans in amplified gastric epithelial lineage progenitors, with accompanying expansion of Hp1 within the glandular epithelium. Lymphoid aggregates that develop in this formerly acid-protected epithelium have molecular features similar to those observed at the forestomach͞glandular junction. These findings demonstrate the important roles played by parietal cells and glycan receptors in determining the positioning of H. pylori within the gastric ecosystem, and emphasize the need to consider the evolution of pathology within a given host in a niche-specific context. gastric acid ͉ adhesin receptors ͉ immune response ͉ germ-free animals A t least half of all humans harbor Helicobacter pylori in their stomachs. This microaerophilic bacterium is usually acquired in childhood and remains in the stomach of its host for decades (1). In most cases, the host-microbial relationship is benign, marked only by mild mucosal inflammation. However, in a subset of individuals, this relationship evolves to produce gastric or duodenal ulcers, adenocarcinoma, or mucosal lymphoma (2).Lee and coworkers (3) have emphasized that severe pathology more often develops in regions of the gastric epithelium where there is a marked transition in the census of acid-producing parietal cells. They and others proposed that local environmental pH gradients at these transitions provide the organism with an opportunity to sample and occupy niches where growth conditions are optimal (3, 4). Once the organism becomes entrenched, pH and other niche-associated factors (e.g., redox state, nutrient availability) then presumably shape the nature of the host-microbial interaction (5).These speculations emphasize the importance of viewing the nature of the host-microbial cross-talk, the genetic microevolution of this bacterium (6, 7), and the structure of the pathogenic cascad...

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Section: Discussionmentioning

confidence: 76%

The impact of parietal cells onHelicobacter pyloritropism and host pathology: An analysis using gnotobiotic normal and transgenic mice

Syder

Guruge

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

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“…Expression profiles were normalized using the GC-RMA method within the GeneSpring GX software (Agilent Technologies, Santa Clara, CA). Expression of genes reported to be enriched in foveolar cells, 39 chief cells, 40 and parietal cells 41 were compared between wild-type and Lkb1…”

Section: Genechip Arrays and Analysis Of Gene Expression Datamentioning

confidence: 99%

Impaired Gastric Gland Differentiation in Peutz-Jeghers Syndrome

Udd

Katajisto

Kyyrönen

et al. 2010

The American Journal of Pathology

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Gastrointestinal hamartomatous polyps in the PeutzJeghers cancer predisposition syndrome and its mouse model (Lkb1؉/؊ ) are presumed to contain all cell types native to the site of their occurrence. This study aimed to explore the pathogenesis of PeutzJeghers syndrome polyposis by characterizing cell types and differentiation of the epithelium of gastric polyps and predisposed mucosa. Both antral and fundic polyps were characterized by a deficit of pepsinogen C-expressing differentiated gland cells (antral gland, mucopeptic, and chief cells); in large fundic polyps, parietal cells were also absent. Gland cell loss was associated with an increase in precursor neck cells, an expansion of the proliferative zone, and an increase in smooth muscle ␣-actin expressing myofibroblasts in the polyp stroma. Lack of pepsinogen C-positive gland cells identified incipient polyps, and even the unaffected mucosa of young predisposed mice displayed an increase in pepsinogen C negative glands (25%; P ‫؍‬ 0045). In addition, in small intestinal polyps, gland cell differentiation was defective, with the absence of Paneth cells. There were no signs of metaplastic differentiation in any of the tissues studied, and both the gastric and small intestinal defects were seen in Lkb1 ؉/؊ mice, as well as polyps from patients with Peutz-Jeghers syndrome. These results identify impaired epithelial differentiation as the earliest pathological sign likely to contribute to tumorigenesis in individuals with inherited Lkb1 mutations. (Am J

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“…In the present report, we describe development of a metastatic NEC from a committed gastric epithelial progenitor that normally gives rise to a lineage that expresses no NE features: the acid-producing parietal cell (PC) (10). This transgenic mouse model is informative because it illustrates how NECs can arise by transdifferentiation of a progenitor normally dedicated to a non-NE fate.…”

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confidence: 99%

“…Acid-producing PCs are unique in that they differentiate within the isthmus. They arise from a committed preparietal cell (pPC) progenitor with well described morphologic features and then undergo a bipolar migration to the pit and base (10,22). The enteroendocrine and caveolated lineages represent the remaining, albeit much less prevalent, cell types (21).…”

mentioning

confidence: 99%

A transgenic mouse model of metastatic carcinoma involving transdifferentiation of a gastric epithelial lineage progenitor to a neuroendocrine phenotype

Syder

Karam

Mills

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

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A molecular profile of the mouse gastric parietal cell with and without exposure to Helicobacter pylori

Cited by 77 publications

References 39 publications

The impact of parietal cells onHelicobacter pyloritropism and host pathology: An analysis using gnotobiotic normal and transgenic mice

The impact of parietal cells onHelicobacter pyloritropism and host pathology: An analysis using gnotobiotic normal and transgenic mice

Impaired Gastric Gland Differentiation in Peutz-Jeghers Syndrome

A transgenic mouse model of metastatic carcinoma involving transdifferentiation of a gastric epithelial lineage progenitor to a neuroendocrine phenotype

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