Reversible drug–induced oxyntic atrophy in rats

Goldenring, James R.; Ray, Gregory S.; Coffey, Robert J.; Meunier, Paul C.; Haley, Patrick J.; Barnes, Tyler; Car, Bruce D.

doi:10.1016/s0016-5085(00)70361-1

Cited by 113 publications

(152 citation statements)

References 38 publications

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“…[31][32][33] We detected basal orientation of the expanding neck cell compartment in H. felis-infected mice, which was accompanied by a profound loss of chief cells. Examples of basaloriented expansion of TFF2-expressing mucous cells accompanying a severe loss of chief cells has also been reported for INS-GAS, 34 DMP777-treated 10 and H. felis-infected 8 mice. Noticeably, hypergastrinemia and oxyntic atrophy are characteristic of all three of these mouse models.…”

Section: Discussionmentioning

confidence: 56%

“…6 Emergence of a prominent mucous cell lineage (the so-called 'mucous cell metaplasia') was found to be one of the earliest histological changes in the fundic mucosa of these mice. 5 Mucosal changes bearing similar features have also been reported in a variety of pathological processes in human and mouse, which include H. pylori infection; [7][8][9] loss of parietal cells upon chemical administration; 10 treatment with a carcinogen, 11 mutation of the Kcnq1 gene encoding a potassium channel, 12 and constitutively active STAT3. 13 This type of mucosal change may therefore represent a common, and possibly reversible 10 response of the stomach, to mucosal injury and tissue inflammation triggered by various stimuli.…”

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confidence: 83%

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Interferon gamma induction of gastric mucous neck cell hypertrophy

Kang

Rathinavelu

Samuelson

et al. 2005

Laboratory Investigation

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Chronic inflammation of the gastric epithelium is believed to induce mucosal changes that can eventually develop into gastric cancer. In gastrin-deficient (GÀ/À) mice exhibiting chronic inflammation in the hypochlorhydric stomach, we documented a prominent fundic mucous cell lineage sharing morphological similarity with preneoplastic changes reported in Helicobacter-infected mice. To study the identity and origin of this cell lineage, we screened for different gastric mucosal cell markers. The clusters of large, foamy cells stained for trefoil factor 2 (TFF2/SP), MUC6 and the lectin Griffonia Simplicifolia II (GSII), but not for the intestine-specific transcription factor Cdx2, suggested that they arise from gastric mucous neck cells. Ki67-labeled GSII-positive neck cells in Helicobacter felis-infected, but not GÀ/À stomachs, suggested that mucous neck cell proliferation accounted for expansion of this compartment in the H. felis model of gastritis, but not the GÀ/À model. Using RNase protection assays and quantitative PCR, we found that interferon gamma (IFNc) was the most abundant proinflammatory cytokine in the GÀ/À stomach. We also found that this Th1 cytokine can increase the abundance of mucous neck cells, since its infusion into mice recapitulated the appearance of these cells as observed in both GÀ/À and H. felis-infected mice. Using the human gastric cell line NCI-N87, we showed that IFNc induces the secretion of mucus and expression of MUC6, TFF2 and pepsinogen II, but not of pepsinogen I and intrinsic factor. In conclusion, our results demonstrate that inflammation, specifically the proinflammatory cytokine IFNc, induced expansion of the fundic mucous neck cell compartment, which likely represents both increased mucus production and cell number.

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Section: Discussionmentioning

confidence: 56%

mentioning

confidence: 83%

Interferon gamma induction of gastric mucous neck cell hypertrophy

Kang

Rathinavelu

Samuelson

et al. 2005

Laboratory Investigation

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“…Because parietal cells are important in regulating complex programs of cellular growth and differentiation in the gastric mucosa, it is not surprising that loss of parietal cells leads to the emergence of metaplastic lineages. Indeed, acute, drug-induced ablation of parietal cells leads to the rapid and reversible development of SPEM (26,27). Studies have pointed to a combination of parietal cell loss and chronic inflammation as necessary for further progression along the metaplasia-dysplasia-cancer pathway (28).…”

Section: Atrophic Gastritis and Gastric Cancermentioning

confidence: 99%

Inflammation, atrophy, and gastric cancer

Fox

Wang²

2007

J. Clin. Invest.

694

626

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The association between chronic inflammation and cancer is now well established. This association has recently received renewed interest with the recognition that microbial pathogens can be responsible for the chronic inflammation observed in many cancers, particularly those originating in the gastrointestinal system. A prime example is Helicobacter pylori, which infects 50% of the world's population and is now known to be responsible for inducing chronic gastric inflammation that progresses to atrophy, metaplasia, dysplasia, and gastric cancer. This Review provides an overview of recent progress in elucidating the bacterial properties responsible for colonization of the stomach, persistence in the stomach, and triggering of inflammation, as well as the host factors that have a role in determining whether gastritis progresses to gastric cancer. We also discuss how the increased understanding of the relationship between inflammation and gastric cancer still leaves many questions unanswered regarding recommendations for prevention and treatment.

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“…11 Since the parietal cell plays a critical role in the differentiation of gastric mucosal lineages, 12,13 the loss of parietal cells is associated with a number of lineage changes, including foveolar hyperplasia, loss of chief cells and mucous cell metaplasia. [14][15][16][17] The normal gastric mucosa includes two types of mucous cells: surface mucous cells secrete trefoil factor family 1 (TFF1) and mucin M1 (MUC5AC), whereas mucous neck cells secrete spasmolytic polypeptide/trefoil factor 2 (SP/ TFF2) and MUC6. A number of investigations in rodents have shown that loss of gastric parietal cells leads to the evolution of SP-expressing metaplasia (SPEM), a gastric fundic metaplastic lineage with TFF2-expressing mucous cells with Brunner's gland or deep antral gland morphology.…”

mentioning

confidence: 99%

“…A number of investigations in rodents have shown that loss of gastric parietal cells leads to the evolution of SP-expressing metaplasia (SPEM), a gastric fundic metaplastic lineage with TFF2-expressing mucous cells with Brunner's gland or deep antral gland morphology. 14,15 While intestinal metaplasia has received the most consideration as a precursor to neoplasia, 18,19 SPEM is also worthy of consideration. In previous studies, we have reported that SPEM is observed in the gastric mucosa adjacent to human gastric cancer.…”

mentioning

confidence: 99%

Emergence of spasmolytic polypeptide-expressing metaplasia in Mongolian gerbils infected with Helicobacter pylori

Yoshizawa

Takenaka

Yamaguchi

et al. 2007

Laboratory Investigation

106

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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.

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Reversible drug–induced oxyntic atrophy in rats

Cited by 113 publications

References 38 publications

Interferon gamma induction of gastric mucous neck cell hypertrophy

Interferon gamma induction of gastric mucous neck cell hypertrophy

Inflammation, atrophy, and gastric cancer

Emergence of spasmolytic polypeptide-expressing metaplasia in Mongolian gerbils infected with Helicobacter pylori

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