Helicobacter pylori-induced PPFIA4 promotes gastritis and gastric bacterial colonization
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE272270 | GEO | 2025/11/11
REPOSITORIES: GEO
Similar Datasets
Project description:Bacterial-modulated gastric epithelial cells (GECs) play key roles in H. pylori-associated pathology. Here we demonstrate a pro-colonization and pro-inflammation role of GEC-expressed glycerol-3-phosphate acyltransferase 3 (GPAT3), a lipid metabolism-associated protein, in H. pylori infection. GPAT3 expression was elevated in gastric mucosa of both patients and mice infected with H. pylori. GPAT3 in GECs was synergistically induced by H. pylori and IL-22 in a cagA-dependent manner. Human gastric GPAT3 correlated with H. pylori colonization and the severity of gastritis, and mouse GPAT3 from non-bone marrow-derived cells promoted bacteria colonization and inflammation. Importantly, H. pylori colonization and inflammation were attenuated in Il22-/-, Gpat3-/- and Il22-/-Gpat3-/- mice. Mechanistically, GPAT3 directly interacted with CCAR1 and activated IKKγ, subsequently promoted NF-κB phosphorylation whereby NF-kB directly bound to the promoters of MMP1, CXCL11 and IL-33 to activate their transcription, which not only led to decreased E-cadherin and zonula occludens-1 proteins by MMP1, thereby resulting in gastric mucosal damage and increased H. pylori colonization; but also resulted in increased gastric influx of CD8+ T cells via CXCL11-dependent migration and their subsequent IL-33-dependent IFN-γ production, thereby promoting H. pylori-associated gastritis. Overall, we propose a model in which GPAT3 collectively ensures H. pylori persistence and promotes gastritis.
2024-04-26 | GSE264450 | GEO
Project description:Helicobacter pylori (H. pylori) infection is characterized as progressive processes of bacterial persistence and chronic gastritis with features of infiltration of mononuclear cells more than granulocytes in gastric mucosa. Angiopoietin-like 4 (ANGPTL4) is considered a double-edged sword in inflammation-associated diseases, but its function and clinical relevance in H. pylori-associated pathology is unknown. Here we demonstrate both pro-colonization and pro-inflammation roles of ANGPTL4 in H. pylori infection. Increased ANGPTL4 in the infected gastric mucosa was produced from gastric epithelial cells (GECs) synergistically induced by H. pylori and IL-17A in a cagA-dependent manner. Human gastric ANGPTL4 correlated with H. pylori colonization and the severity of gastritis, and mouse ANGPTL4 from non-bone marrow-derived cells promoted bacteria colonization and inflammation. Importantly, H. pylori colonization and inflammation were attenuated in Il17a-/-, Angptl4-/-, Il17a-/-Angptl4-/- mice. Mechanistically, ANGPTL4 bound to integrin αV (ITGAV) on GECs to suppress CXCL1 production by inhibiting ERK, leading to decreased gastric influx of neutrophils, thereby promoting H. pylori colonization; ANGPTL4 also bound to ITGAV on monocytes to promote CCL5 production by activating PI3K-AKT-NF-κB, resulting in increased gastric influx of regulatory CD4+ T cells (Tregs) via CCL5-CCR4-dependent migration. In turn, ANGPTL4 induced Treg proliferation through binding to ITGAV to activate PI3K-AKT-NF-κB, promoting H. pylori-associated gastritis. Overall, we propose a model in which ANGPTL4 collectively ensures H. pylori persistence and promotes gastritis. Efforts to inhibit ANGPTL4-associated pathway may prove valuable strategies in treating H. pylori infection.
2024-05-15 | GSE266891 | GEO
Project description:H. pylori infection of human gastric epithelial cells (GEC) represses H,K-ATPase alpha subunit (HK-alpha) gene transcription through NF-Kappa B p50 homodimer binding to HK-alpha promoter. The bacterial cagA and slt gene products have been implicated in HK-alpha repression, which facilitates gastric H. pylori colonization and may underlie transient clinical hypochlorhydria. We hypothesized that H. pylori also regulates H,K-ATPase expression post-transcriptionally by micro-RNA interaction with HK-alpha mRNA. Our microarray experiment examined the effect of infection by wildtype H. pylori infection or a delta-cagA H. pylori mutant on miRNA expression of human gastric cells (AGS). Our results indicate that H. pylori infection up-regulates GEC miRNAs that target the HK-alpha 3' UTR and block translation, and that CagA activity is implicated in the miRNA up-regulation.
2016-01-18 | GSE51306 | GEO
Project description:H. pylori infection of human gastric epithelial cells (GEC) represses H,K-ATPase alpha subunit (HK-alpha) gene transcription through NF-Kappa B p50 homodimer binding to HK-alpha promoter. The bacterial cagA and slt gene products have been implicated in HK-alpha repression, which facilitates gastric H. pylori colonization and may underlie transient clinical hypochlorhydria. We hypothesized that H. pylori also regulates H,K-ATPase expression post-transcriptionally by micro-RNA interaction with HK-alpha mRNA. Our microarray experiment examined the effect of infection by wildtype H. pylori infection or a delta-cagA H. pylori mutant on miRNA expression of human gastric cells (AGS). Our results indicate that H. pylori infection up-regulates GEC miRNAs that target the HK-alpha 3' UTR and block translation, and that CagA activity is implicated in the miRNA up-regulation. Three types of samples were generated for microarray analysis: 1) AGS cells infected with wildtype H. pylori; 2) AGS cells infected with cagA-deficient H. pylori; 3) a mock-infected sample, prepared as a control by combining total RNA from uninfected AGS cells with total RNA from wildtype H. pylori, with relative eukaryotic and prokaryotic RNA amounts matching those observed in infected samples, based on proportional ribosomal peak heights quantified by Bioanalyzer. Three experimental replicates were generated for each type of treatment.
2016-01-18 | E-GEOD-51306 | biostudies-arrayexpress
Project description:Helicobacter pylori (H. pylori) is a human pathogen that infects almost half of the world’s population. Infection with H. pylori is frequently associated with chronic gastritis and can even lead to gastric and duodenal ulcers and gastric cancer. Although the persistent colonization of H. pylori and the development of H. pylori-associated gastritis remain poorly understood, it is believed that, in gastric mucosa, the modulated gastric epithelial cells (GECs) by H. pylori are key contributors. We used microarrays to detail the global programme of gene expression in Helicobacter pylori infected-gastric epithelial cell line AGS cells and identified up-regulated genes induced by Helicobacter pylori infection.
2024-04-18 | GSE264263 | GEO
Project description:Colonization of the human stomach with cag pathogenicity island (PAI)-positive H. pylori strains is associated with increased gastric cancer risk compared to colonization with cag PAI-negative strains. To evaluate the contributions of the Cag type IV secretion system (T4SS) and CagA (a secreted bacterial oncoprotein) to gastric molecular alterations relevant for carcinogenesis, we infected Mongolian gerbils with a Cag T4SS-positive wild-type (WT) H. pylori strain, one of two Cag T4SS mutant strains (∆cagT or ∆cagY), or a ∆cagA mutant for 12 weeks. Histologic staining revealed a biphasic distribution of gastric inflammation severity (either minimal or severe) in WT-infected animals and minimal inflammation in mutant-infected animals. Atrophic gastritis (a premalignant condition), dysplasia, and gastric adenocarcinoma were only detected in WT-infected animals with high inflammation scores. Transcriptional profiling and analyses of micro-extracted tryptic peptides (LC-MS/MS and imaging mass spectrometry) revealed more than a thousand molecular alterations in gastric tissues from WT-infected animals with high inflammation scores compared to uninfected tissues and few alterations in tissues from other groups of infected animals. Proteins with altered abundance in animals with severe Cag T4SS-induced inflammation mapped to multiple pathways, including the complement/coagulation cascade and proteasome pathway. Proteins exhibiting markedly increased abundance in tissues from H. pylori-infected animals with severe inflammation included calprotectin components, lysozyme, lactoferrin, superoxide dismutase, eosinophil peroxidase, proteins involved in proteasome activation, STAT1, TrpRS, GBP2, and IIGP1. These results demonstrate key roles for CagA and Cag T4SS activity in promoting gastric mucosal inflammation, transcriptional alterations, and proteomic alterations relevant to gastric carcinogenesis.
2025-02-28 | PXD060632 | Pride
Project description:Helicobacter pylori (H. pylori) is a type of pathogen in humans that has infected nearly half of the population worldwide. Infections with H. pylori are typically associated with chronic gastritis and may even lead to gastric and duodenal ulcers and stomach cancer. While the mechanisms behind persistent colonization by H. pylori and the development of gastritis associated with it remain unclear, it is generally believed that the gastric epithelial cells (GECs) modulated by H. pylori in the gastric mucosa play a crucial role. We extensively studied the global gene expression patterns in H. pylori-infected AGS cells, a line of gastric epithelial cells, and identified genes that show increased expression upon infection with H. pylori.
2024-11-25 | GSE282738 | GEO
Project description:Background: Helicobacter pylori has been shown to alter the secretion of gastric hormones that modulate body fat deposition. Since cag-positive H. pylori strains interact intimately with the host gastric epithelial cells and trigger higher inflammation than cag-negative strains, we hypothesized that gastric colonization with H. pylori strains without functional cagA ameliorates obesity and its complications by modulating gastric gene expression and inflammation. Methodology/Principal Findings: To test this hypothesis we examined the effects of gastric colonization on metabolic and inflammatory markers in mice infected with two isogenic strains of H. pylori: 26695 strain 98-325 (cagA+ wild-type) and its cag pathogenicity island (cagPAI) mutant strain 99-305, a knockout made by inserting a chloramphenicol resistance cassette. Only the cagPAI mutant decreased fasting blood glucose levels, improved glucose tolerance and suppressed weight gain in db/db mice and mice with diet-induced obesity. These effects were associated with increased gastric leptin levels, suppressed infiltration of macrophages, enhanced influx of regulatory T cells (Treg) in adipose tissue and suppressed gastric inflammation. Gene set enrichment analyses of gastric mucosal samples identified six differentially modulated pathways, including the Hedgehog signaling pathway that is associated with control of cellular proliferation and gastric carcinogenesis as well as the insulin signaling pathway. Conclusions/Significance: Gastric colonization with cagPAI-negative strains of H. pylori ameliorate obesity and inflammation by modulating gastric gene expression, suggesting that cag-negative H. pylori strains might be beneficial in ameliorating obesity and its co-morbidities. Gastric mucosa from three groups of mice: uninfected, infected with H. pylori 26695 strain 98-325 (cagA+ wild-type) or infected with H. pylori mutant strain 99-305 (lacking cag pathogenicity island; cagA-)
2010-11-13 | E-GEOD-21833 | biostudies-arrayexpress
Project description:Helicobacter pylori colonization of the human stomach is a strong risk factor for gastric cancer. To investigate H. pylori-induced gastric molecular alterations, we used a Mongolian gerbil model of gastric carcinogenesis. Histologic evaluation revealed varying levels of atrophic gastritis (a premalignant condition characterized by parietal and chief cell loss) in H. pylori-infected animals, and transcriptional profiling revealed a loss of markers for these cell types. We then assessed the spatial distribution and relative abundance of proteins in the gastric tissues using imaging mass spectrometry and liquid chromatography with tandem mass spectrometry (LC-MS/MS). We detected striking differences in protein content of corpus and antrum tissues. 492 proteins were preferentially localized to the corpus in uninfected animals. The abundance of 91 of these proteins was reduced in H. pylori-infected corpus tissues exhibiting atrophic gastritis compared to infected corpus tissues with non-atrophic gastritis or uninfected corpus tissues; these included numerous proteins with metabolic functions. Fifty proteins localized to the corpus in uninfected animals were diffusely delocalized throughout the stomach in infected tissues with atrophic gastritis; these included numerous proteins with roles in protein processing. Corresponding alterations were not detected in animals infected with a H. pylori ∆cagT mutant (lacking Cag type IV secretion system activity). These results indicate that H. pylori can cause loss of proteins normally localized to the gastric corpus as well as diffuse delocalization of corpus-specific proteins, resulting in marked changes in the normal gastric molecular partitioning into distinct corpus and antrum regions.
2023-12-04 | PXD046333 | Pride
Project description:In this study, we aimed to reveal whether gastric mucosa with AIG has a specific gene expression profile, involving in its histology and chronic inflammation. To approach this, we performed comprehensive analysis of gene expression using gastric mucosa with atuoimmune gastritis, that with H. pylori-associated gastritis and healthy mucosa without any inflammation. Potential mechanisms of the gene expression changes in gastric mucosa with AIG were also explored.
2024-01-01 | GSE233973 | GEO