Dataset Information

HpSlyD inducing CDX2 and VIL1 expression mediated through TCTP protein may contribute to intestinal metaplasia in the stomach.

ABSTRACT: Helicobacter pylori infection is the most important risk factor for gastric intestinal metaplasia (IM). Our previous study demonstrated that infection with H. pylori HpslyD-positive strains associated with IM. To further investigate the signalling pathway involved in HpSlyD-induced IM, CDX2 and VIL1 expressions were determined before and after HpSlyD application. TCTP was knocked down by siRNA or overexpressed by plasmid transfection. An HpSlyD binding protein was used to block HpSlyD's enzymatic activity. The expression of CDX2 and TCTP in gastric diseases was measured by immunohistochemistry. Our results showed HpSlyD induced CDX2 and VIL1 expressions. TCTP protein expression was markedly increased after application of HpSlyD and in an HpSlyD-expressing stable cell line. Downregulation of TCTP protein led to decreased HpSlyD-induced CDX2 and VIL1. Overexpression of TCTP protein improved the expression of CDX2 and VIL1. Co-application of HpSlyD and FK506 led to significant reductions in CDX2, VIL1, and TCTP expression. Immunohistochemistry demonstrated that CDX2 and TCTP expression was higher in HpslyD-positive specimens compared with HpslyD-negative ones. Expression of CDX2 was positively correlated with TCTP in HpslyD-positive cells. Our study is the first to show that HpSlyD induction of CDX2 and VIL1 expression mediated through TCTP may contribute to IM in the stomach.

SUBMITTER: Li Q

PROVIDER: S-EPMC5442128 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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HpSlyD inducing CDX2 and VIL1 expression mediated through TCTP protein may contribute to intestinal metaplasia in the stomach.

Li Qiuping Q Zhu Yanmei Y Liu Jun J Yu Xiuwen X Chen Moye M Dong Nannan N Gong Yuehua Y Yuan Yuan Y

Scientific reports 20170523 1

Helicobacter pylori infection is the most important risk factor for gastric intestinal metaplasia (IM). Our previous study demonstrated that infection with H. pylori HpslyD-positive strains associated with IM. To further investigate the signalling pathway involved in HpSlyD-induced IM, CDX2 and VIL1 expressions were determined before and after HpSlyD application. TCTP was knocked down by siRNA or overexpressed by plasmid transfection. An HpSlyD binding protein was used to block HpSlyD's enzymati ...[more]

PMID: 28536478

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Project description:Helicobacter pylori is a well-recognized bacterium associated with the development of several histopathological lesions in the stomach. The chronic infection produces an inflammatory lesion known as gastritis. This lesion can later progress to more serious lesions such as intestinal metaplasia. Some attempts in the transcriptome of these conditions have been made; these however, have yielded limited information. Given the potential of high-throughput technologies for understanding biological processes altered and in the description of biomarkers of disease, we performed a genome-wide gene expression analysis in gastric biopsies. The aim of this study was to describe the altered molecular mechanism and potential biomarkers of follicular gastritis, chronic gastritis and intestinal metaplasia, through the identification of characteristic gene expression profiles in each histopathological lesion. The exploratory set comprised twenty-one biopsies from patients with follicular gastritis (n=7), chronic gastritis (n=7), and intestinal metaplasia (n=7), which were analyzed by whole-genome gene expression microarrays. The enrichment analyses and functional annotation of genes using computational tools were performed. The bioinformatics data of the same 21 biopsies were validated by real time PCR analysis while 79 FFPE samples were analyzed by immunohistochemistry. Gene expression analyses showed profiles for each histopathological lesion. Follicular gastritis had an expression profile with marked enrichment of immunologically-related genes. In contrast, chronic gastritis was characterized by a deregulation of mitochondrial-related genes and a down regulation of genes associated with protection against oxidative stress. Meanwhile, intestinal metaplasia showed an over expression of gastrointestinal stem cell markers and molecules related to RNA metabolism. Our results provide a comprehensive and reliable gene expression analysis of follicular gastritis, chronic gastritis and intestinal metaplasia disorders. The gene expression patterns described established a clear difference between the three pathologies studied and allowed the identification of several potential biomarkers for each histological change.

Project description:Background & Aims: Tissue metaplasia is uncommon in adults because established cis-element programs resist rewiring. In Barrett’s esophagus, the distal esophageal mucosa acquires predominantly intestinal character, with notable gastric features, and is predisposed to develop invasive cancers. We sought to understand the chromatin underpinnings of Barrett’s metaplasia and why it commonly displays simultaneous gastric and intestinal properties. Methods: We profiled cis-regulatory elements with active histone modifications in primary human biopsy materials using chromatin immunoprecipitation followed by DNA sequencing (ChIP-seq). Mutations in Barrett’s esophagus were examined in relation to tissue-specific enhancer landscapes using a random-forest machine learning algorithm. We also profiled open chromatin at single-cell resolution in primary Barrett’s biopsy specimens using the assay for transposase-accessible chromatin (ATAC-seq). We used one- and two-color immunohistochemistry to examine protein expression of tissue-restricted genes. Results: Barrett’s esophagus bears epigenome fingerprints of human stomach and intestinal columnar, but not esophageal squamous, epithelia. Mutational patterns were best explained as arising on the epigenome background of active gastric cis-elements, supporting the view that adjoining stomach epithelium is a likely tissue source. Individual cells in Barrett’s metaplasia co-express gastric and intestinal genes, reflecting concomitant chromatin access at enhancers ordinarily restricted to one or the other epithelium. Protein expression of stomach-specific mucins, CLDN18, and a novel gastric marker, ANXA10, revealed extensive tissue and sub-clonal heterogeneity of dual stomach-intestinal cell states. Conclusions: These findings reveal mixed and dynamic tissue-restricted chromatin states and phenotypic heterogeneity in Barrett’s esophagus. Pervasive intra-gland variation argues against stem-cell governance of this phenotype.

Dataset Information

HpSlyD inducing CDX2 and VIL1 expression mediated through TCTP protein may contribute to intestinal metaplasia in the stomach.

Publications

HpSlyD inducing CDX2 and VIL1 expression mediated through TCTP protein may contribute to intestinal metaplasia in the stomach.

Similar Datasets

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