scholarly journals Effect of Helicobacter pylori on Tight Junctions in Gastric Epithelia

2021 ◽  
Author(s):  
Erika Patricia Rendón-Huerta ◽  
Carlos Abraham García-García ◽  
Luis Felipe Montaño Estrada
Keyword(s):  
Tight Junctions ◽  
Molecular Complexes ◽  
Erk Signaling ◽  
Cancer Development ◽  
Epithelial Barrier ◽  
Caga Gene ◽  
Neoplastic Tissue ◽  
Cag Pathogenicity Island ◽  
New Concepts ◽  
H Pylori

Molecular complexes grouped under the names of tight, adherent or gap junction regulate the flow of water, ions and macromolecules through epithelium paracellular spaces. The main constituents of tight junctions are claudins, a family of 26 different proteins whose expression and distribution are tissue specific but varies in tumors. A change in claudin 1, 3, 4, 5, 6, 7, 9 and 18 expression, that contributes to lose epithelial cohesion, has been associated to enhanced cell proliferation, migration, and invasiveness in gastric neoplastic tissue. Chronic inflammation process induced by H. pylori infection, a major risk factor for gastric cancer development, disrupts tight junctions via CagA gene, Cag pathogenicity island, and VacA, but the effect upon the epithelial barrier of H. pylori lipopolysaccharides or H. pylori-induced up-regulation of mTOR and ERK signaling pathways by microRNA-100 establishes new concepts of proof.

scholarly journals Role of TNF-α-Inducing Protein Secreted by Helicobacter pylori as a Tumor Promoter in Gastric Cancer and Emerging Preventive Strategies

Toxins ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 181
Author(s):  
Masami Suganuma ◽  
Tatsuro Watanabe ◽  
Eisaburo Sueoka ◽  
In Kyoung Lim ◽  
Hirota Fujiki
Keyword(s):  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
Cell Surface Receptor ◽  
Tumor Promoter ◽  
Cancer Development ◽  
Human Gastric Cancer ◽  
Tnf Α ◽  
Surface Receptor ◽  
H Pylori ◽  
Factor Α

The tumor necrosis factor-α (TNF-α)-inducing protein (tipα) gene family, comprising Helicobacter pylori membrane protein 1 (hp-mp1) and tipα, has been identified as a tumor promoter, contributing to H. pylori carcinogenicity. Tipα is a unique H. pylori protein with no similarity to other pathogenicity factors, CagA, VacA, and urease. American H. pylori strains cause human gastric cancer, whereas African strains cause gastritis. The presence of Tipα in American and Euro-Asian strains suggests its involvement in human gastric cancer development. Tipα secreted from H. pylori stimulates gastric cancer development by inducing TNF-α, an endogenous tumor promoter, through its interaction with nucleolin, a Tipα receptor. This review covers the following topics: tumor-promoting activity of the Tipα family members HP-MP1 and Tipα, the mechanism underlying this activity of Tipα via binding to the cell-surface receptor, nucleolin, the crystal structure of rdel-Tipα and N-terminal truncated rTipα, inhibition of Tipα-associated gastric carcinogenesis by tumor suppressor B-cell translocation gene 2 (BTG2/TIS21), and new strategies to prevent and treat gastric cancer. Thus, Tipα contributes to the carcinogenicity of H. pylori by a mechanism that differs from those of CagA and VacA.

scholarly journals Ras Mutation Impairs Epithelial Barrier Function to a Wide Range of Nonelectrolytes

2005 ◽  
Vol 16 (12) ◽  
pp. 5538-5550 ◽  
Author(s):  
James M. Mullin ◽  
James M. Leatherman ◽  
Mary Carmen Valenzano ◽  
Erika Rendon Huerta ◽  
Jon Verrechio ◽  
...  
Keyword(s):  
Tight Junctions ◽  
Mitogen Activated Protein Kinase ◽  
Epithelial Barrier ◽  
Epithelial Barrier Function ◽  
Downstream Effects ◽  
Extracellular Signal ◽  
Wide Range ◽  
Mitogen Activated Protein ◽  
Protein Kinase Signaling ◽  
Kinase Signaling Pathway

Although ras mutations have been shown to affect epithelial architecture and polarity, their role in altering tight junctions remains unclear. Transfection of a valine-12 mutated ras construct into LLC-PK1 renal epithelia produces leakiness of tight junctions to certain types of solutes. Transepithelial permeability of d-mannitol increases sixfold but transepithelial electrical resistance increases >40%. This indicates decreased paracellular permeability to NaCl but increased permeability to nonelectrolytes. Permeability increases to d-mannitol (Mr 182), polyethylene glycol (Mr 4000), and 10,000-Mr methylated dextran but not to 2,000,000-Mr methylated dextran. This implies a “ceiling” on the size of solutes that can cross a ras-mutated epithelial barrier and therefore that the increased permeability is not due to loss of cells or junctions. Although the abundance of claudin-2 declined to undetectable levels in the ras-overexpressing cells compared with vector controls, levels of occludin and claudins 1, 4, and 7 increased. The abundance of claudins-3 and -5 remained unchanged. An increase in extracellular signal-regulated kinase-2 phosphorylation suggests that the downstream effects on the tight junction may be due to changes in the mitogen-activated protein kinase signaling pathway. These selective changes in permeability may influence tumorigenesis by the types of solutes now able to cross the epithelial barrier.

scholarly journals The organization of Helicobacter pylori cag-pathogenicity island (cagPAI) genes in multiracial population with histopathological changes of gastric mucosa

2019 ◽  
Author(s):  
Alfizah Hanafiah ◽  
Shaza Azlin Razak ◽  
Hui-min Neoh ◽  
Noraziah Mohamad Zin ◽  
Bruno S. Lopes
Keyword(s):  
Helicobacter Pylori ◽  
Gastric Mucosa ◽  
Pathogenicity Island ◽  
Type Iv Secretion ◽  
Virulence Determinants ◽  
Gastric Diseases ◽  
Cag Pathogenicity Island ◽  
Type Iv ◽  
Inflammatory Score ◽  
H Pylori

Abstract Background: Helicobacter pylori is a Gram-negative bacillus that colonises only the mucus layer of the human stomach and is implicated in gastric diseases. Virulent H. pylori harbouring cag-pathogenicity island (cagPAI) which encodes genes for type IV secretion system (T4SS) and CagA protein is one of the major virulence determinants involved in disease development. We examined the entire cagPAI genes in 95 H. pylori isolates from a multiracial population and examined the intactness of cagPAI region with histopathological scores of the gastric mucosa. Results: 95.8% of H. pylori isolates were cagPAI-positive with 23.2% having an intact cagPAI, whereas 72.6% had a partial/rearranged cagPAI. In our study, cag2 and cag4 were found to be significantly higher in H. pylori isolated from Malays, whereas cag4 was predominant in Chinese isolates. We also detected cag24 in significantly high proportion in isolates from the Malays and the Indians compared to the Chinese isolates. The intactness of cagPAI region showed an association with histopathological scores of the gastric mucosa. Significant association was observed between H. pylori harbouring partial cagPAI and higher density of H. pylori and neutrophil activity, whereas strains which lacked cagPAI was associated with higher inflammatory score. Conclusions: The screening of the entire cagPAI genes provides an accurate overview of the cagPAI organisation in H. pylori isolates in a multiracial population. The genotypes of H. pylori strains with various cagPAI rearrangement associated with patients’ ethnicities and histopathological scores might contribute to the pathogenesis of H. pylori infection in a multi-ethnic population.

scholarly journals Risk assessment of pathological conditions caused by circulating H. pylori strains

2020 ◽  
Vol 46 (1) ◽  
pp. 60-64
Author(s):  
D. K. Karimova ◽  
G. N. Sobirova ◽  
M. M. Karimov
Keyword(s):  
Gastric Cancer ◽  
Repetitive Sequences ◽  
Fold Increase ◽  
Caga Gene ◽  
Repetitive Region ◽  
Polymorphic Gene ◽  
C Segments ◽  
H Pylori ◽  
Gastroduodenal Zone ◽  
Gene Data

In recent years, there has been an increase in the prevalence of inflammatory and destructive diseases of the gastroduodenal zone, which is primarily explained by Helicobacter pylori (H. pylori) infection. One of the main factors of H. pylori pathogenicity is presence of cytotoxin-associated gene — CagA. It is known that CagA-positive H. pylori strains are associated with the development of atrophy, tumor invasion and rapid metastasis. A number of recently published studies have revealed that CagA is a polymorphic gene which contains a different number of repetitive sequences located in the 3’ region. Each repetitive region of CagA contains Glu-Pro-Ile-Tyr-Ala (EPIYA) profiles including tyrosine phosphorylation. Depending on the sequence of the EPIYA profile, there are 4 segments: EPIYA-A, EPIYA-B, EPIYA-C, EPIYA-D, each containing a repetitive region. Geographical features of the prevalence of H. pylori strains depending on the sequence of EPIYA have been revealed: EPIYA-A region of the western isolates of this bacterium is associated with EPIYA-A, EPIYA-B, EPIYA-C segments, while the eastern CagA-positive H. pylori isolates are characterized by the A-B-D type of the CagA gene. Data illustrating the strong correlation between the western CagA-positive H. pylori strains, which have a repeating EPIYA-C segment, and the development of precancerous states, as well as gastric cancer, are presented. H. pylori strains containing simultaneously A-B motives of EPIYA or one C-type of the CagA gene are associated with a 7-fold increase of risk of gastric cancer compared to CagA-negative strains; presence of two or more EPIYA-C motives is associated with a 30-fold increase of this risk.

scholarly journals Translocation of Pseudomonas aeruginosa from the Intestinal Tract Is Mediated by the Binding of ExoS to an Na,K-ATPase Regulator, FXYD3

2010 ◽  
Vol 78 (11) ◽  
pp. 4511-4522 ◽  
Author(s):  
Jun Okuda ◽  
Naoki Hayashi ◽  
Masashi Okamoto ◽  
Shinji Sawada ◽  
Shu Minagawa ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Tight Junctions ◽  
Intestinal Tract ◽  
Transmembrane Domain ◽  
Epithelial Barrier ◽  
Comparative Genomic ◽  
Intestinal Epithelial ◽  
Intestinal Epithelial Barrier ◽  
Gut Colonization ◽  
Bacterial Penetration

ABSTRACT The intestinal tract is considered the most important reservoir of Pseudomonas aeruginosa in intensive care units (ICUs). Gut colonization by P. aeruginosa underlies the development of invasive infections such as gut-derived sepsis. Intestinal colonization by P. aeruginosa is associated with higher ICU mortality rates. The translocation of endogenous P. aeruginosa from the colonized intestinal tract is an important pathogenic phenomenon. Here we identify bacterial and host proteins associated with bacterial penetration through the intestinal epithelial barrier. We first show by comparative genomic hybridization analysis that the exoS gene, encoding the type III effector protein, ExoS, was specifically detected in a clinical isolate that showed higher virulence in silkworms following midgut injection. We further show using a silkworm oral infection model that exoS is required both for virulence and for bacterial translocation from the midgut to the hemolymph. Using a bacterial two-hybrid screen, we show that the mammalian factor FXYD3, which colocalizes with and regulates the function of Na,K-ATPase, directly binds ExoS. A pulldown assay revealed that ExoS binds to the transmembrane domain of FXYD3, which also interacts with Na,K-ATPase. Na,K-ATPase controls the structure and barrier function of tight junctions in epithelial cells. Collectively, our results suggest that ExoS facilitates P. aeruginosa penetration through the intestinal epithelial barrier by binding to FXYD3 and thereby impairing the defense function of tight junctions against bacterial penetration.

H. pylori-encoded CagA disrupts tight junctions and induces invasiveness of AGS gastric carcinoma cells via Cdx2-dependent targeting of Claudin-2

2013 ◽  
Vol 286 (1-2) ◽  
pp. 22-30 ◽  
Author(s):  
Xin Song ◽  
Hui-Xin Chen ◽  
Xiao-Yan Wang ◽  
Xi-Yun Deng ◽  
Yin-Xue Xi ◽  
...  
Keyword(s):  
Gastric Carcinoma ◽  
Tight Junctions ◽  
Carcinoma Cells ◽  
H Pylori

scholarly journals theLiTE™: A Screening Platform to Identify Compounds that Reinforce Tight Junctions

2022 ◽  
Vol 12 ◽  
Author(s):  
Teresa Lopes Gomes ◽  
Virgínia de Oliveira-Marques ◽  
Richard John Hampson ◽  
António Jacinto ◽  
Luciana Vieira de Moraes ◽  
...  
Keyword(s):  
Tight Junctions ◽  
Food Supplement ◽  
Epithelial Barrier ◽  
Barrier Dysfunction ◽  
Epithelial Barrier Function ◽  
Selective Permeability ◽  
Egg Chambers ◽  
Screening Platform ◽  
And Control ◽  
Further Development

Tight junctions (TJ) are formed by transmembrane and intracellular proteins that seal the intercellular space and control selective permeability of epithelia. Integrity of the epithelial barrier is central to tissue homeostasis and barrier dysfunction has been linked to many pathological conditions. TJ support the maintenance of cell polarity through interactions with the Par complex (Cdc42-Par-6-Par-3-aPKC) in which Par-6 is an adaptor and links the proteins of the complex together. Studies have shown that Par-6 overexpression delays the assembly of TJ proteins suggesting that Par-6 negatively regulates TJ assembly. Because restoring barrier integrity is of key therapeutic and prophylactic value, we focus on finding compounds that have epithelial barrier reinforcement properties; we developed a screening platform (theLiTE™) to identify compounds that modulate Par-6 expression in follicular epithelial cells from Par-6-GFP Drosophila melanogaster egg chambers. Hits identified were then tested whether they improve epithelial barrier function, using measurements of transepithelial electrical resistance (TEER) or dye efflux to evaluate paracellular permeability. We tested 2,400 compounds, found in total 10 hits. Here we present data on six of them: the first four hits allowed us to sequentially build confidence in theLiTE™ and two compounds that were shortlisted for further development (myricetin and quercetin). We selected quercetin due to its clinical and scientific validation as a compound that regulates TJ; food supplement formulated on the basis of this discovery is currently undergoing clinical evaluation in gastroesophageal reflux disease (GERD) sufferers.

scholarly journals Nasal Epithelial Barrier Integrity and Tight Junctions Disruption in Allergic Rhinitis: Overview and Pathogenic Insights

2021 ◽  
Vol 12 ◽  
Author(s):  
Siti Muhamad Nur Husna ◽  
Hern-Tze Tina Tan ◽  
Norasnieda Md Shukri ◽  
Noor Suryani Mohd Ashari ◽  
Kah Keng Wong
Keyword(s):  
Allergic Rhinitis ◽  
Tight Junctions ◽  
Lymphoid Cells ◽  
Cell Junctions ◽  
Epithelial Barrier ◽  
Epigenetic Changes ◽  
T Helper ◽  
Therapeutic Approaches ◽  
First Line ◽  
T Helper 2

Allergic rhinitis (AR) is a common disorder affecting up to 40% of the population worldwide and it usually persists throughout life. Nasal epithelial barrier constitutes the first line of defense against invasion of harmful pathogens or aeroallergens. Cell junctions comprising of tight junctions (TJs), adherens junctions, desmosomes and hemidesmosomes form the nasal epithelial barrier. Impairment of TJ molecules plays causative roles in the pathogenesis of AR. In this review, we describe and discuss the components of TJs and their disruption leading to development of AR, as well as regulation of TJs expression by epigenetic changes, neuro-immune interaction, epithelial-derived cytokines (thymic stromal lymphopoietin, IL-25 and IL-33), T helper 2 (Th2) cytokines (IL-4, IL-5, IL-6 and IL-13) and innate lymphoid cells. These growing evidence support the development of novel therapeutic approaches to restore nasal epithelial TJs expression in AR patients.

scholarly journals MiR-873-5p: A Potential Molecular Marker for Cancer Diagnosis and Prognosis

2021 ◽  
Vol 11 ◽  
Author(s):  
Yuhao Zou ◽  
Chenming Zhong ◽  
Zekai Hu ◽  
Shiwei Duan
Keyword(s):  
Molecular Marker ◽  
Cancer Diagnosis ◽  
Target Genes ◽  
Erk Signaling ◽  
Cancer Development ◽  
Epigenetic Factors ◽  
Potential Value ◽  
Diagnosis And Prognosis ◽  
Anti Cancer ◽  
Cancer Diagnosis And Prognosis

miR-873 is a microRNA located on chromosome 9p21.1. miR-873-5p and miR-873-3p are the two main members of the miR-873 family. Most studies focus on miR-873-5p, and there are a few studies on miR-873-3p. The expression level of miR-873-5p was down-regulated in 14 cancers and up-regulated in 4 cancers. miR-873-5p has many targeted genes, which have unique molecular functions such as catalytic activity, transcription regulation, and binding. miR-873-5p affects cancer development through the PIK3/AKT/mTOR, Wnt/β-Catenin, NF-κβ, and MEK/ERK signaling pathways. In addition, the target genes of miR-873-5p are closely related to the proliferation, apoptosis, migration, invasion, cell cycle, cell stemness, and glycolysis of cancer cells. The target genes of miR-873-5p are also related to the efficacy of several anti-cancer drugs. Currently, in cancer, the expression of miR-873-5p is regulated by a variety of epigenetic factors. This review summarizes the role and mechanism of miR-873-5p in human tumors shows the potential value of miR-873-5p as a molecular marker for cancer diagnosis and prognosis.

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