Alterations in junctional proteins, inflammatory mediators and extracellular matrix molecules in eosinophilic esophagitis

Abdulnour‐Nakhoul, Solange; Al-Tawil, Youhanna; Gyftopoulos, Alex; Brown, Karen; Hansen, Molly; Butcher, Kathy F.; Eidelwein, Alexandra; Noel, R. Adam; Rabon, E.; Posta, Allison; Nakhoul, Nazih L.

doi:10.1016/j.clim.2013.05.004

Cited by 56 publications

(47 citation statements)

References 46 publications

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“…This study demonstrates that: (1) DSG1 is more than 20 times downregulated in active EoE compared with controls; (2) DSG1 deficiency of the oesophageal mucosa leads to a structural alteration of the mucosa; and (3) active EoE is associated with a disturbed mucosal integrity. These findings have been confirmed in an independent study showing that, in children with active EoE, the expression of the intercellular junction proteins E-cadherin and claudin-1 is reduced 12. This is now accepted as confirmation that, in active EoE, the mucosal integrity is altered due to defects in desmosomal and tight junction adhesion proteins.…”

Section: Aetiopathogenesissupporting

confidence: 54%

Update on basic and clinical aspects of eosinophilic oesophagitis

Straumann¹,

Schoepfer

2014

Gut

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Section: Aetiopathogenesissupporting

confidence: 54%

Update on basic and clinical aspects of eosinophilic oesophagitis

Straumann¹,

Schoepfer

2014

Gut

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“…The first is that the maintenance of the epithelial barrier is associated with restoration of tight junction structures and increased expression of tight junction proteins (47,48). The second possibility is that the inflammatory mediators secreted by virus-infected cells play important roles in the modification of tight junction protein expression (25,49,50).…”

Section: Discussionmentioning

confidence: 99%

Tight Junction Protein Occludin Is a Porcine Epidemic Diarrhea Virus Entry Factor

Luo

Guo

Zhang

et al. 2017

J Virol

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Porcine epidemic diarrhea virus (PEDV), the causative agent of porcine epidemic diarrhea, has caused huge economic losses in pig-producing countries. Although PEDV was long believed to replicate in the intestinal epithelium by using aminopeptidase N as a receptor, the mechanisms of PEDV infection are not fully characterized. In this study, we found that PEDV infection of epithelial cells results in disruption of the tight junctional distribution of occludin to its intracellular location. Overexpression of occludin in target cells makes them more susceptible to PEDV infection, whereas ablation of occludin expression by use of small interfering RNA (siRNA) in target cells significantly reduces their susceptibility to virus infection. However, the results observed with occludin siRNA indicate that occludin is not required for virus attachment. We conclude that occludin plays an essential role in PEDV infection at the postbinding stages. Furthermore, we observed that macropinocytosis inhibitors blocked occludin internalization and virus entry, indicating that virus entry and occludin internalization are closely coupled. However, the macropinocytosis inhibitors could not impede virus replication once the virus had entered host cells. This suggests that occludin internalization by macropinocytosis or a macropinocytosis-like process is involved in the virus entry events. Immunofluorescence confocal microscopy showed that PEDV was trapped at cellular junctional regions upon macropinocytosis inhibitor treatment, indicating that occludin may serve as a scaffold in the vicinity of virus entry. Collectively, these data show that occludin plays an essential role in PEDV infection during late entry events. Our observation may provide novel insights into PEDV infection and related pathogenesis.IMPORTANCE Tight junctions are highly specialized membrane domains whose main function is to attach adjacent cells to each other, thereby forming intercellular seals. Here we investigate, for the first time, the role of the tight junction protein occludin in PEDV infection. We observed that PEDV infection induced the internalization of occludin. By using genetic modification methods, we demonstrate that occludin plays an essential role in PEDV infection. Moreover, PEDV entry and occludin internalization seem to be closely coupled. Our findings reveal a new mechanism of PEDV infection.KEYWORDS PEDV, occludin, tight junction C oronaviruses are a group of positive-strand RNA viruses belonging to the family Coronaviridae in the order Nidovirales. They are broadly distributed among mammalian and avian species, and they cause acute and persistent infections. In most cases, coronaviruses are generally associated with significant respiratory and/or intestinal tract diseases (1, 2). Porcine epidemic diarrhea virus (PEDV) has been identified as the etiologic agent of porcine epidemic diarrhea (PED), and it causes diarrhea, vomiting, and dehydration in infected swine (3, 4). Outbreaks of PED have occurred frequently in

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“…Since the esophageal mucosal barrier is disrupted in EoE, the expression of TJ proteins in the esophagus was evaluated, and CLDN1 expression that was evaluated using immunohistochemistry was down-regulated [45,46]. The barrier function of esophageal mucosa in EoE might be regulated by Th2 cytokines and filaggrin [47,48].…”

Section: Eosinophilic Esophagitis (Eoe)mentioning

confidence: 99%

Gastrointestinal mucosal barrier function and diseases

2016

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The gastrointestinal mucosal barrier plays an essential role in the separation of the inside of the body from the outside environment. Tight junctions (TJs) are the most important component for construction of a constitutive barrier of epithelial cells, and they regulate the permeability of the barrier by tightly sealing the cell-cell junctions. TJ proteins are represented by claudins, occludin, junctional adhesion molecules, and scaffold protein zonula occludens. Among these TJ proteins, claudins are the major components of TJs and are responsible for the barrier and the polarity of the epithelial cells. Gastrointestinal diseases including reflux esophagitis, inflammatory bowel disease, functional gastrointestinal disorders, and cancers may be regulated by these molecules, and disruption of their functions leads to chronic inflammatory conditions and chronic or progressive disease. Therefore, regulation of the barrier function of epithelial cells by regulating the expression and localization of TJ proteins is a potential new target for the treatment of these diseases. Treatment strategies for these diseases might thus be largely altered if symptom generation and/or immune dysfunction could be regulated through improvement of mucosal barrier function. Since TJ proteins may also modify tumor infiltration and metastasis, other important goals include finding a good TJ biomarker of cancer progression and patient prognosis, and developing TJ protein-targeted therapies that can modify patient prognosis. This review summarizes current understanding of gastrointestinal barrier function, TJ protein expression, and the mechanisms underlying epithelial barrier dysregulation in gastrointestinal diseases.

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Alterations in junctional proteins, inflammatory mediators and extracellular matrix molecules in eosinophilic esophagitis

Cited by 56 publications

References 46 publications

Update on basic and clinical aspects of eosinophilic oesophagitis

Update on basic and clinical aspects of eosinophilic oesophagitis

Tight Junction Protein Occludin Is a Porcine Epidemic Diarrhea Virus Entry Factor

Gastrointestinal mucosal barrier function and diseases

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