Dissociation and dispersion of claudin-3 from the tight junction could be one of the most sensitive indicators of reflux esophagitis in a rat model of the disease

Oguro, Masako; Koike, Masato; Ueno, Takashi; Asaoka, Daisuke; Mori, Hiroki; Nagahara, Akihito; Uchiyama, Yasuo; Watanabe, Sumio

doi:10.1007/s00535-011-0390-1

Cited by 30 publications

(38 citation statements)

References 27 publications

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“…1B) as compared with control rats (Fig. 1A), which is consistent with previous reports (Asaoka et al, 1995;Oguro et al, 2011). Because claudin-3 is mainly distributed in the lower part of the epithelium of the esophagus in control rats , we first performed detailed electron microscopic observations in the stratum basale (SB) and stratum spinosum (SS) of the esophageal epithelia in the control and RE groups using ultra-thin sections (Fig.…”

Section: Transmission Electron Microscopic Observation Of the Esophagsupporting

confidence: 89%

“…In control rats, claudins-1, -3, and -4 were located on the surface of esophageal epithelial cells. In rats with RE, the expression of claudin-1 or -4 was not changed significantly whereas that of claudin-3 was substantially decreased (Asaoka et al, 2005;Oguro et al, 2011). In addition, we previously showed that gastric acid-induced dissociation of claudin-3 was associated with instability of the epithelial TJ complex, as demonstrated by sedimentation analysis using centrifugation in a sucrose density gradient .…”

Section: Animalsmentioning

confidence: 91%

“…Chronic acid RE was induced in rats using a modified version of the model described in previous reports (Omura et al, 1999;Asaoka et al, 2005;Oguro et al, 2011). Briefly, animals (8 weeks old) were fasted for 24 h prior to surgery.…”

Section: Induction Of Chronic Acid Reflux Esophagitis In Ratsmentioning

confidence: 99%

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<b>Ultrastructural analyses of the rat esophageal stratified epithelium under normal conditions and in chronic reflux esophagitis </b>

Mori

Koike

Gotow

et al. 2011

Archives of Histology and Cytology

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TJ structures only in the stratum granulosum (SG) of the esophageal epithelia in control rats, and the number of TJ structures seemed to be decreased in the RE model.Most of the TJs were composed of only one ＂kissing point.＂ Freeze-fracture electron microscopy did not allow identification of typical TJ strands, suggesting that TJs in the rat esophageal mucosa were not well-developed. Immunoelectron microscopy confirmed our previous immunohistochemical results indicating that claudin-3 was located on the surface of esophageal epithelial cells in control rats and that the immunoreactivity decreased in the RE group. However, claudin-3 was diffusely localized on the plasma membrane and not concentrated on the TJ structures. These results indicate that claudin-3 is not directly involved in the composition of the TJ structure.

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Section: Transmission Electron Microscopic Observation Of the Esophagsupporting

confidence: 89%

Section: Animalsmentioning

confidence: 91%

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<b>Ultrastructural analyses of the rat esophageal stratified epithelium under normal conditions and in chronic reflux esophagitis </b>

Mori

Koike

Gotow

et al. 2011

Archives of Histology and Cytology

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“…In the present experiments involving acidic bile salts, the levels of claudin-1 and -4 in the insoluble fraction significantly decreased following treatment with acidic GCA or TCA. Although claudin-3 has been detected in rat esophagus and claudin-18 has been detected in Barrett's esophageal epithelia (17,23,27), claudin-3 and claudin-18 were not detected in normal human esophagus or ALI-cultured cultured HEECs. As a limitation of the present study, although we previously detected the delocalization of claudin-4 in both colonic epithelial cell model and stratified epithelial cell model with NHBE cells after stimulation (29,31), differences in the staining pattern of TJ proteins after acidic bile acid stimulation were not detected in our HEECs model.…”

Section: Discussionmentioning

confidence: 93%

Bile salts disrupt human esophageal squamous epithelial barrier function by modulating tight junction proteins

Chen

Oshima

Shan

et al. 2012

American Journal of Physiology-Gastrointestinal and Liver Physi

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of acid and bile acids contributes to epithelial tissue injury in gastro-esophageal reflux disease. However, the influence of refluxed material on human esophageal stratified epithelial barrier function and tight junction (TJ) proteins has not been fully elucidated. Here, we investigated the influence of acid and bile acids on barrier function and TJ protein distribution using a newly developed air-liquid interface (ALI) in vitro culture model of stratified squamous epithelium based on primary human esophageal epithelial cells (HEECs). Under ALI conditions, HEECs formed distinct epithelial layers on Transwell inserts after 7 days of culture. The epithelial layers formed TJ, and the presence of claudin-1, claudin-4, and occludin were detected by immunofluorescent staining. The NP-40-insoluble fraction of these TJ proteins was significantly higher by day 7 of ALI culture. Exposure of HEECs to pH 2, and taurocholic acid (TCA) and glycocholic acid (GCA) at pH 3, but not pH 4, for 1 h decreased transepithelial electrical resistance (TEER) and increased paracellular permeability. Exposure of cell layers to GCA (pH 3) and TCA (pH 3) for 1 h also markedly reduced the insoluble fractions of claudin-1 and -4. We found that deoxycholic acid (pH 7.4 or 6, 1 h) and pepsin (pH 3, 24 h) significantly decreased TEER and increased permeability. Based on these findings, ALIcultured HEECs represent a new in vitro model of human esophageal stratified epithelium and are suitable for studying esophageal epithelial barrier functions. Using this model, we demonstrated that acid, bile acids, and pepsin disrupt squamous epithelial barrier function partly by modulating TJ proteins. These results provide new insights into understanding the role of TJ proteins in esophagitis. esophageal epithelium; claudin; air-liquid interface THE HUMAN ESOPHAGUS IS LINED with a layer of nonkeratinizing stratified squamous epithelium, which serves as an effective barrier against the influx of luminal contents. The esophageal epithelium consists of the basal, suprabasal, and superficial layers (14). In the pathogenesis of reflux esophagitis, acids, bile acids, and pepsin play a major role in damaging the esophageal epithelium (34). However, the mechanisms by which the luminal contents affect the barrier function of the stratified epithelial cell layers remain unclear.Tight junctions (TJs) separate the apical and basolateral cell surface domains to establish cell polarity and establish barrier function. TJs are composed of several proteins, including occludin, claudins, junctional adhesion molecule (22), and the scaffold protein zonula occludens (ZO). Of these proteins, claudins, which form specialized cellular structures that regulate the permeability of cellular layers, are the most important structural and functional components of TJ strands (1,6,10,30). Claudins are an integral transmembrane protein family consisting of at least 27 subtypes in mammals (22,40) and are essential for establishing and maintaining epithelial cell polarity by controlling the m...

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“…Complicated expression patterns of various CLDNs in different species make the data confusing. For example, CLDN3 was detected in a rat esophagus, and it has been reported to be modulated in rat esophageal disorders including reflux esophagitis [19][20][21][22]. However, CLDN3 is not detectable in the human esophagus, suggesting that, if it is expressed, it must be expressed at a very low level.…”

Section: The Interpretation Of Tj Formation and Expression Patternsmentioning

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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Dissociation and dispersion of claudin-3 from the tight junction could be one of the most sensitive indicators of reflux esophagitis in a rat model of the disease

Abstract: Our data indicate that the dispersion of claudin-3 from esophageal epithelial plasma membranes to cytoplasm and the resulting instability of the TJ complex could be one of the most specific and sensitive indicators for monitoring inflammatory and recovery processes in RE.

Cited by 30 publications

References 27 publications

<b>Ultrastructural analyses of the rat esophageal stratified epithelium under normal conditions and in chronic reflux esophagitis </b>

<b>Ultrastructural analyses of the rat esophageal stratified epithelium under normal conditions and in chronic reflux esophagitis </b>

Bile salts disrupt human esophageal squamous epithelial barrier function by modulating tight junction proteins

Gastrointestinal mucosal barrier function and diseases

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