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Dysregulated mRNA and miRNA expression networks in Helicobater pylori infected gastric epithelial cell line, AGS (mRNA)

ABSTRACT: We performed genome-wide mRNA and miRNA expression analysis in gastric epithelial cell line AGS infected with Helicobacter pylori at 100 Multiplicity of Infection (MOI), comparing the expression profile of infected cells with uninfected cells. Differentially expressed mRNAs and miRNAs wered identified, which showed a 1.5 fold change in expression in infected cells compared to uninfected cells. We performed in silico analysis of miRNA-mRNA target interactions among the inversely correlated differentially expressed miRNAs and mRNAs, and performed functional enrichment analysis of the target genes, to identify important cellular pathways that reflect the patho-biology of H. pylori infected cells. Among the important miRNA-mRNA target pairs, PHLPP1, reported to be associated with poor prognosis in cancer, was predicted to be a putative target of miR-29b-1-5p. Therefore, we focused on the miR-29b-1-5p/PHLPP1 miRNA/target pair for detailed investigation into their role in H. pylori-mediated signalling in gastric epithelial cells. This study demonstrates that an integrated analysis of global mRNA and miRNA expression patterns, combined with miRNA-mRNA target prediction and functional analysis of miRNA target genes can yield an understanding of the critical pathways regulating the behaviour of gastric epithelial cells challenged with H. pylori.

ORGANISM(S): Homo sapiens

PROVIDER: GSE108305 | GEO | 2017/12/20

SECONDARY ACCESSION(S): PRJNA423068

REPOSITORIES: GEO

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Dysregulated mRNA and miRNA expression networks in Helicobacter pylori infected gastric epithelial cell line, AGS (miRNA)

Project description:We performed genome-wide mRNA and miRNA expression analysis in gastric epithelial cell line AGS infected with Helicobacter pylori at 100 Multiplicity of Infection (MOI), comparing the expression profile of infected cells with uninfected cells. Differentially expressed mRNAs and miRNAs were identified, which showed a 1.5 fold change in expression in infected cells compared to uninfected cells. We performed in silico analysis of miRNA-mRNA target interactions among the inversely correlated differentially expressed miRNAs and mRNAs, and performed functional enrichment analysis of the target genes, to identify important cellular pathways that reflect the patho-biology of H. pylori infected cells. Among the important miRNA-mRNA target pairs, PHLPP1, reported to be associated with poor prognosis in cancer, was predicted to be a putative target of miR-29b-1-5p. Therefore, we focused on the miR-29b-1-5p/PHLPP1 miRNA/target pair for detailed investigation into their role in H. pylori-mediated signalling in gastric epithelial cells. This study demonstrates that an integrated analysis of global mRNA and miRNA expression patterns, combined with miRNA-mRNA target prediction and functional analysis of miRNA target genes can yield an understanding of the critical pathways regulating the behaviour of gastric epithelial cells challenged with H. pylori.

2017-12-20 | GSE108306 | GEO

Helicobacter pylori-induced changes in miRNA expression in human gastric epithelial cells

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

Remodeling of the gastric environment in Helicobacter pylori-induced atrophic gastritis

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

Helicobacter pylori infection dysregulates gastric proteome

Project description:The purpose of the study was to define gastric cell-specific proteomic changes, induced by H. pylori oncogenic strains, that are critical for initiation of the gastric carcinogenic cascade. Gastric cell scrapings were harvested from H. pylori-infected and uninfected animals for quantitative proteomic analyses using isobaric tags for relative and absolute quantitation (iTRAQ). Canonical and disease pathway mapping using Ingenuity Pathway Analysis (IPA) identified significantly altered inflammatory and cancer-signaling pathways that included Rab/Ras signaling proteins.

2018-11-23 | PXD009583 | Pride

Toll-like receptor 10 in Helicobacter pylori infection

Project description:Helicobacter pylori is a highly successful and important human pathogen that causes chronic gastritis, peptic ulcer diseases and gastric cancer. Innate immunity plays an important role of the primary defense against pathogens and epidemiological studies have suggested a role of toll-like receptor 1 (TLR1) in the risk of H. pylori acquisition. We performed microarray analysis of gastric mucosal biopsy specimens from H. pylori-positive and uninfected subjects; infection was associated with an ~15-fold up-regulation of TLR10 (p <0.001). Quantitative RT-PCR confirmed TLR10 mRNA levels were increased 3-fold in H. pylori-infection (p <0.001) and immunohistochemistory using anti-TLR10 polyclonal antibodies showed increased TLR10 expression in gastric epithelial cells of infected individuals. In vitro experiments where H. pylori was co-cultured with NCI-N87 gastric cells showed significant H. pylori-specific up-regulation of TLR10 mRNA levels and a correlation with TLR2 mRNA levels (R = 0.87, P <0.001). We compared combinations of TLRs for their ability to mediate NF-_B activation. NF-_B activation was increased following exposure to heat killed H. pylori or H. pylori-LPS only with the TLR2/TLR10 heterodimer. These findings suggest TLR10 is a functional receptor involved in the innate immune response to H. pylori infection and that TLR2/TLR10 heterodimer possibly functions in the recognition of H. pylori-LPS.

2015-06-01 | GSE60427 | GEO

Transcription profiling of Helicobacter pylori-infected mouse gastric epithelial progenitor and non-progenitor cells.

Project description:Helicobacter pylori clinical isolates can establish themselves in gastric epithelial stem cells and this interaction may have implications for gastric tumorigenesis. Mouse gastric epithelial progenitor cells (mGEPs) and non-progenitor gastric epithelial cells (npGECs) were infected for 24hrs with Helicobacter pylori clinical isolates Kx1 and Kx2. Kx1 was isolated from a patient with chronic atrophic gastritis (ChAG) and Kx2 from the same patient 4 years later, when he progressed to gastric adenocarcinoma. Experiment Overall Design: mGEPs and npGECs were seeded and grown to 70% confluency in RPMI1640 medium supplemented with 10% FBS before being infected with H. pylori strains Kx1 or Kx2 that had been grown to log phase. After 24h, media and non-attached bacteria were washed off and the cells harvested by trypsinization. RNA was prepared from triplicate cultures of mGEP cells infected with Kx1 or Kx2, npGECs infected with Kx1 or Kx2 and uninfected mGEPs and npGECs that served as controls.

2008-04-07 | E-GEOD-10262 | biostudies-arrayexpress

Helicobacter pylori-induced changes in miRNA expression in human gastric epithelial cells

2016-01-18 | GSE51306 | GEO

Ornithine Decarboxylase in Gastric Epithelial Cells Promotes the Immunopathogenesis of Helicobacter pylori Infection

Project description:Colonization by H. pylori is associated with a wide range of gastric diseases, ranging from superficial gastritis to more severe pathologies, including intestinal metaplasia and adenocarcinoma. The interplay of the host response and the pathogen affect the outcome of disease. One major component of the mucosal response to H. pylori is the activation of a strong, but inefficient immune response that fails to control the infection and frequently causes tissue damage. We have shown that polyamines can regulate H. pylori-induced inflammation. Chemical inhibition of ornithine decarboxylase (ODC), which generates putrescine from L-ornithine, reduces gastritis in mice and adenocarcinoma incidence in gerbils infected with H. pylori. However, we have also demonstrated that Odc deletion in myeloid cells enhances M1 macrophage activation and gastritis. Here we used a genetic approach to assess the specific role of gastric epithelial ODC during H. pylori infection. Deletion of Odc in gastric epithelial cells reduces gastritis, attenuates epithelial proliferaton, alters the metabolome, and dowregulates the expression of immune mediators induced by H. pylori. Inhibition of ODC activity in gastric epithelial cells reduces H. pylori-induced NF-B activation and CXCL8 mRNA expression. Chronic inflammation is a major risk factor for the progression to more severe pathologies associated with H. pylori infection and we now show that epithelial ODC plays an important role in mediating this inflammatory response.

2022-06-15 | MTBLS3235 | MetaboLights

Helicobacter pylori colonization ameliorates glucose homeostasis in mice

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

Helicobacter pylori pathogenic mechanism

Project description:Helicobacter pylori infection reprograms host gene expression and influences various cellular processes, which have been investigated by cDNA microarray in vitro culture cells and in vivo patients of the chronic abdominal complaint. In this study，the effects of H. pylori infection on host gene expression in the gastric antral mucosa of patients with chronic gastritis were examined. The gastric antral mucosa was obtained from a total of 6 untreated patients undergoing gastroscopic and pathologic confirmation of chronic superficial gastritis. Three patients infected by H. pylori and 3 patients uninfected were used to cDNA microarray experiment.

2012-04-29 | E-GEOD-30042 | biostudies-arrayexpress

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