Proteomic and transcriptomic studies of BCG823 cells stimulated with Helicobacter pylori isolates from gastric MALT lymphoma
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE148112 | GEO | 2020/04/07
REPOSITORIES: GEO
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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: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.
2010-11-13 | GSE21833 | GEO
Project description:The genome of the gastric pathogen Helicobacter pylori harbors a remarkably low number of regulatory genes, including three and five open reading frames encoding two-component histidine kinases and response regulators, respectively, which are putatively involved in transcriptional regulation. Inactivation of the response regulator gene hp1021 resulted in a severe growth defect, as indicated by a small-colony phenotype. Recently we found that phosphorylation of the receiver domain HP1021 is not needed for its response regulator function and may not occur at all. No target genes have been identified so far. In this study we define the HP1021-dependent regulon consisting of 79 genes (51 activated, 28 repressed) by global transcriptional profiling of an HP1021-deficient H. pylori mutant. Transcriptome analyses were performed using a whole-genome microarray containing 1649 PCR products generated with specific primer pairs derived from the genome sequences of H. pylori 26695 (Tomb et al., 1997. The complete genome sequence of the gastric pathogen Helicobacter pylori. Nature 388:539-547) and J99 (Alm et al., 1999. Genomic-sequence comparison of two unrelated isolates of the human gastric pathogen Helicobacter pylori. Nature 397:176-180) which were spotted in duplicate. Microarrays were produced as described by Gressmann et al. (Gressmann et al., 2005. Gain and loss of multiple genes during the evolution of Helicobacter pylori. PLoS Genet 1(4):e43). To determine genes which are differentially expressed in the HP1021-deficient mutant 26695/1021::km, cDNA was prepared from RNA extracted from H. pylori 26695 WT and 26695/1021::km. A total of eight RNA samples from two independent RNA preparations from strain 26695 WT and 26695/HP1021::km, respectively, was used for cDNA labelling und hybridisation. Dye reversal colour swaps were performed as follows: one cDNA sample was generated using Cy3-dCTP and the other using Cy5-dCTP resulting in four labelled cDNAs per colour swap. Cy5-dCTP and Cy3-dCTP labelled cDNAs were combined and hybridized to the H. pylori microarray. The slides were scanned using ScanArray HT and analysed by using the ScanArray express software (Perkin Elmer, version 3.0). Spots were flagged and eliminated from analysis when the signal to background ratio was less then three or in obvious instances of high background or stray fluorescent signals. Median intensities of spots were background corrected and differences in dye bias were normalized by using the LOWESS algorithm (Yang et al., 2002. Normalization for cDNA microarray data: a robuste composite method addressing single and multiple slide systematic variation. Nucleic Acid Res. 30:e15). The signal ratios as measure of differential expression between the red and green channels were obtained from processed signal intensities. Ratios were further analysed with Microsoft Excel (Microsoft) and SAM software for statistic significance (Tusher et al., 2001. Significance analysis of microarrays applied to the ionizing radiation response. Proc. Natl. Acad. Sci. USA 98:5116-5121). To determine the significance of differential expression RNA was isolated from the H. pylori 26695 WT grown in BHI broth, and 20 µg of this RNA were labelled either with Cy3-dCTP or with Cy5-dCTP. The two cDNA probes generated were hybridized onto the same slide, and the data were analysed as mentioned above. Signal ratios < 0.5 and > 2.0 were analyzed further.
2010-07-01 | E-GEOD-5971 | biostudies-arrayexpress
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
Project description:Helicobacter pylori enhances the risk for ulcer disease and gastric cancer, yet only a minority of H. pylori-colonized individuals develop disease. We examined the ability of two H. pylori isolates to induce differential host responses in vivo or in vitro, and then used an H. pylori whole genome microarray to identify bacterial determinants related to pathogenesis. Gastric ulcer strain B128 induced more severe gastritis, proliferation, and apoptosis in gerbil mucosa than did duodenal ulcer strain G1.1, and gastric ulceration and atrophy occurred only in B128+ gerbils. In vitro, gerbil-passaged B128 derivatives significantly increased IL-8 secretion and apoptosis compared with G1.1 strains. DNA hybridization to the microarray identified several strain-specific differences in gene composition including a large deletion of the cag pathogenicity island in strain G1.1. Partial and complete disruption of the cag island in strain B128 attenuated induction of IL-8 in vitro and significantly decreased gastric inflammation in vivo. These results indicate that the ability of H. pylori to regulate epithelial cell responses related to inflammation depends on the presence of an intact cag pathogenicity island. Use of an H pylori whole genome microarray is an effective method to identify differences in gene content between H. pylori strains that induce distinct pathological outcomes in a rodent model of H. pylori infection. Set of arrays organized by shared biological context, such as organism, tumors types, processes, etc. Computed
2005-08-16 | E-GEOD-3135 | biostudies-arrayexpress
Project description:Causes gastric inflammation and peptic ulcer disease
| PRJNA234 | ENA
Project description:Causes gastric inflammation and peptic ulcer disease
| PRJNA233 | ENA
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. Keywords: RNA Expression Array
2008-02-22 | GSE10262 | GEO
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) were infected for 24hrs with Helicobacter pylori clinical isolates Kx1 and Kx2. Kx1 and Kx2 were also grown in cell media in the absence of cells. 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. Keywords: RNA Expression Array
2008-02-22 | GSE10261 | GEO