Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Effects of a gastrin receptor antagonist (NTZ, previously named YF) on the gastric corpus mucosa of HKATPase betasubunit knockout (KO) mice

ABSTRACT: Purpose: the effects of a gastrin receptor antagonist has been studies in patients with gastrin neuroendocrine (NE) tumours due to hypergastrinemia. This mouse model of hypergastrinemia is a model for studying long term acid inhibition, including NE hyperplasia and formation of Spasmolytic polypeptide expressing metaplasia (SPEM), a proposed premalignant alteration of the stomach. Methods: RNA was isolated from the oxyntic mucosa. RNA was sequenced using standard Illumina protocols on a NextSeq 500 instrument. Results: NTZ reduced oxyntic mucosal hypertropohy and stomach weight. Neuroendocrine cell hyperplasia and NE markers were also reduced. Spasmolytic polypeptide expressing metaplasia (SPEM) was expressed in KO mice and was not affected by the gastrin receptor antagonist. Conclusions: The gastrin receptor antagonist YF reduced gastric corpus mucosal hypertrophy and NE cell hyperplasia in HKATPase KO mice, but did not affect SPEM or SPEM related genes.

ORGANISM(S): Mus musculus

PROVIDER: GSE142513 | GEO | 2019/12/23

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Endogenous glucocorticoids suppress spontaneous gastric inflammation and spasmolytic polypeptide expressing metaplasia

Project description:Adrenalectomy induced severe eosinophil and macrophage infiltration localized to the gastric corpus resulting in development of spasmolytic polypeptide expressing metaplasia (SPEM) and oxyntic atrophy. RNA sequencing analysis revealed significant upregulation of proinflammatory genes 3 days post-adrenalectomy, prior to leukocyte infiltration and histopathological changes.

2019-03-20 | GSE107736 | GEO

Tristetraprolin prevents gastric metaplasia by suppressing pathogenic inflammation

Project description:Purpose: The goals of this study are to examine whether TTP can protect the stomach from adrenalectomy (ADX)-induced gastric inflammation and spasmolytic polypeptide-expressing metaplasia (SPEM). Methods: we utilized the TTP∆ARE mouse model to examine whether TTP overexpression can protect the stomach from adrenalectomy (ADX)-induced gastric inflammation and spasmolytic polypeptide-expressing metaplasia (SPEM). Results: We found that TTP∆ARE mice were completely protected from ADX-induce gastric inflammation and SPEM. RNA sequencing revealed that TTP overexpression suppressed the expression of genes associated with the innate immune response. Finally, we show that protection from gastric inflammation was only partially due to suppression of Tnf, a well-known TTP target. Conclusions: Our results demonstrate that TTP exerts broad anti-inflammatory effects in the stomach, and suggest that therapies that increase TTP expression may be effective treatments of pro-neoplastic gastric inflammation.

2021-11-10 | GSE164349 | GEO

IL-33 regulates metaplasia and macrophage polarization in the stomach.

Project description:Alternatively-activated macrophages (M2) are known to play a critical role in intestinalization of spasmolytic polypeptide-expressing metaplasia (SPEM), which is a precursor to gastric adenocarcinoma. However, the precise mechanism(s) and critical mediators produced by M2 macrophages that lead to SPEM are unknown. Using established murine models of metaplasia in the stomach, the aim of the present study was to determine how M2 macrophages induce intestinalized SPEM. Macrophages from the stomach corpus of mice with SPEM (DMP-777-treated) or advanced intestinalized SPEM (L635-treated) were isolated and RNA sequencing was performed. IL-33 was the most upregulated cytokine in macrophages associated with intestinalized SPEM. L635-treated IL-33 knock out mice did not develop metaplasia, suggesting that IL-33 is required for the induction of SPEM after acute parietal cell loss. While the loss of IL-33 did not reduce macrophage recruitment into the mucosa, infiltrating macrophages were not M2 polarized. We conclude that IL-33 is necessary for both the induction of mucous metaplasia (SPEM) in the stomach and polarization towards M2 in recruited macrophages. Our data suggest that the inflammatory pathway in the stomach after parietal cell loss resembles pathways associated with allergy-induced airway inflammation, which implicates novel treatment options for gastritis patients to prevent gastric cancer.

2017-01-20 | GSE77195 | GEO

Transplantation of gastric organoid-derived spasmolytic polypeptide/TFF2-expressing metaplasia (SPEM) cell lineage promotes ulcer repair in the aged stomach

Project description:Background & Aims: Spasmolytic polypeptide/TFF2-expressing metaplasia (SPEM) is known to emerge following parietal cell loss and during Helicobacter pylori infection, however its role in gastric ulcer repair is unknown. Therefore, we sought to investigate if SPEM plays a role in epithelial regeneration. Methods: Acetic acid ulcers were induced in young (2-3 months) C57BL/6 mice to determine the quality of ulcer repair. Gastric tissue was collected and analyzed to determine the expression of SPEM within the regenerating epithelium. As a comparison to native tissue the expression of SPEM was also identified within cultured gastric mouse-derived organoids. Results: Wound healing in the mice coincided with the emergence of SPEM expressing CD44v within the ulcerated region. The emergence of SPEM was also observed in cultured gastric organoids. Conclusions: These data demonstrate the SPEM may play a role in epithelial regeneration. Conclusions: These data demonstrate the SPEM may play a role in epithelial regeneration. 4 samples were used for ulcerated and uninjured tissue. 1 sample was used for intact tissue and organoid-derived RNA. The 'Ulcerated' samples represent C57BL/6 mice with ulcers and the 'Uninjured' samples represent the healthy controls (for "ulcerated" samples). The "Intact stomach tissue" and "Gastric organoids" samples are other types of samples that compared separately. "Gastric organoids" in this comparison are derived from "Intact stomach tissue".

2015-09-23 | E-GEOD-73336 | biostudies-arrayexpress

Expression data from acutely damaged stomachs

Project description:Tamoxifen injection injures the mouse stomach, triggering a plastic regenerative response termed Spasmolytic Polypeptide Exressing Metaplasia. We are probing how tamoxifen treated stomachs differ from healthy controls, and also how injected rapamycin affects this process

2018-02-15 | GSE103570 | GEO

Protein Kinase A (PKAc alpha ) regulates gastric homeostasis and preneoplastic lesions

Project description:We generated a novel Six2-Cre+/-PKAcaRfl/wt (CA-PKA) CA-PKA mouse in which expression of constitutive-active PKAcaR was induced in gastric mesenchyme progenitors. CA-PKA mice showed disruption of gastric homeostasis characterized by aberrant mucosal development and epithelial hyperproliferation; ultimately developing multiple features of gastric corpus preneoplasia including decreased parietal cells, mucous cell hyperplasia, spasmolytic peptide expressing metaplasia (SPEM) with intestinal characteristics and dysplastic and invasive cystic glands. Our results show that constitutively active PKAcaR in the stomach mesenchyme nonautonomously disrupts gastric homeostasis characterized by increased epithelial proliferation and aberrant epithelial maldevelopment, ultimately leading to gastric preneoplasia.

2022-09-20 | GSE196236 | GEO

Interleukin 27 Protects From Gastric Atrophy and Metaplasia During Chronic Autoimmune Gastritis

Project description:Background & Aims: The association between chronic inflammation and gastric carcinogenesis is well established, but it is not clear how immune cells and cytokines regulate this process. We investigated the role of interleukin 27 (IL27) in the development of gastric atrophy, hyperplasia, and metaplasia (preneoplastic lesions associated with inflammation-induced gastric cancer) in mice with autoimmune gastritis. Methods: We performed studies with TxA23 mice (control mice), which express a T-cell receptor against the H+/K+ adenosine triphosphatase α chain and develop autoimmune gastritis, and TxA23xEbi3-/- mice, which develop gastritis but do not express IL27. In some experiments, mice were given high-dose tamoxifen to induce parietal cell atrophy and spasmolytic polypeptide-expressing metaplasia (SPEM). Recombinant IL27 was administered to mice with mini osmotic pumps. Stomachs were collected and analyzed by histopathology and immunofluorescence; we used flow cytometry to measure IL27 and identify immune cells that secrete IL27 in the gastric mucosa. Single-cell RNA sequencing was performed on immune cells that infiltrated stomach tissues. Results: We identified IL27-secreting macrophages and dendritic cell in the corpus of mice with chronic gastritis (TxA23 mice). Mice deficient in IL27 developed more severe gastritis, atrophy, and SPEM than control mice. Administration of recombinant IL27 significantly reduced the severity of inflammation, atrophy, and SPEM in mice with gastritis. Single-cell RNA sequencing showed that IL27 acted almost exclusively on stomach-infiltrating CD4+ T cells to suppress expression of inflammatory genes. Conclusions: In studies of mice with autoimmune gastritis, we found that IL27 is an inhibitor of gastritis and SPEM, suppressing CD4+ T-cell–mediated inflammation in the gastric mucosa.

2024-10-01 | GSE278552 | GEO

Transcriptional analysis reveals the molecular details of atrophic gastritis in Helicobacter pylori infected corpus mucosa

Project description:The majority of gastric cancer cases are believed to be caused by chronic infection with the bacterium Helicobacter pylori, and atrophic corpus gastritis is a predisposing condition to gastric cancer development. We aimed to increase understanding of the molecular details of atrophy by performing a global transcriptome analysis of stomach tissue. Biopsies from patients with different stages of H. pylori infection were taken from both the antrum and corpus mucosa and analyzed on microarrays. The stages included patients without current H. pylori infection, H. pylori-infected without corpus atrophy and patients with current or past H. pylori-infection with corpus-predominant atrophic gastritis.Using clustering and integrated analysis, we found firm evidence for antralization of the corpus mucosa of atrophy patients. This antralization harbored gain of gastrin expression, as well as loss of expression of corpus-related genes, such as genes associated with acid production, energy metabolism and blood clotting. The analyses provided detailed molecular evidence for simultaneous intestinal metaplasia (IM) and spasmolytic polypeptide expressing metaplasia (SPEM) in atrophic corpus tissue. Finally, acidic mammalian chitinase, a chitin-degrading enzyme produced by chief cells, was shown to be strongly down-regulated in corpus atrophy.Transcriptome analysis revealed several gene groups which are related to development of corpus atrophy, some of which were increased also in H. pylori-infected non-atrophic patients. Furthermore, loss of acidic chitinase expression is a promising marker for corpus atrophy. Biopsies from well classified patients with different stages of H. pylori infection were taken from both the antrum and corpus mucosa. These stages included H. pylori un-infected, H. pylori-infected without corpus atrophy and H. pylori-infected with corpus-predominant atrophic gastritis.

2014-02-04 | E-GEOD-27411 | biostudies-arrayexpress

Transplantation of gastric organoid-derived spasmolytic polypeptide/TFF2-expressing metaplasia (SPEM) cell lineage promotes ulcer repair in the aged stomach

2015-09-23 | GSE73336 | GEO

Transcriptional analysis reveals the molecular details of atrophic gastritis in Helicobacter pylori infected corpus mucosa

2014-02-04 | GSE27411 | GEO