Acidic bile salts modulate the squamous epithelial barrier function by modulating tight junction proteins

Chen, Xin; Oshima, Tadayuki; Tomita, Toshihiko; Fukui, Hirokazu; Watari, Jiro; Matsumoto, Takayuki; Miwa, Hiroto

doi:10.1152/ajpgi.00096.2011

Cited by 50 publications

(49 citation statements)

References 36 publications

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“…Occludin was not expressed in basal layers (Fig. 2) [12]. These findings indicate that the localization of TJs in the esophagus is different from the location of dilated intercellular spaces (DISs), which will be discussed in the following section, and which are important for determining the real barrier of the esophagus.…”

Section: Tjs In the Esophagusmentioning

confidence: 86%

“…In evaluating the function of esophageal epithelial layers, we originally established esophageal stratified epithelial cell layers in vitro [12][13][14][15][16]. When we observed the development of stratified epithelial layers, we found that the barrier was dramatically developed 5 to 7 days after air-liquid interface (ALI)-culture of primary human squamous epithelial cells [15].…”

Section: Tjs In the Esophagusmentioning

confidence: 99%

“…These claudin subtypes are expressed in an organ-specific manner and regulate the tissue-specific physiological functions of TJs [4]. Based on sequence similarity, CLDN1-10, 14, 15, 17 and 19 are called classic CLDNs, and 12,13,16,18,29 and 24 are called non-classic CLDNs [9].…”

Section: Introductionmentioning

confidence: 99%

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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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Section: Tjs In the Esophagusmentioning

confidence: 86%

Section: Tjs In the Esophagusmentioning

confidence: 99%

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Gastrointestinal mucosal barrier function and diseases

2016

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“…We recently established an esophageal-like stratified epithelial cell layer under ALI conditions using NHBE cells. 9,15 Although the cells were not originally from the esophagus, these cells created stratified epithelial layers, expressed cytokeratins like the esophagus, and the TJ expression pattern and gene expression pattern were similar to human esophagus. 9 Here, the stratified epithelial cell layers acquired more than 1500 O .…”

Section: Discussionmentioning

confidence: 99%

Acid modulates the squamous epithelial barrier function by modulating the localization of claudins in the superficial layers

Oshima

Koseki

Chen

et al. 2012

Laboratory Investigation

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Acid is a major cause of gastro-esophageal reflux disease. However, the influence of acid on the esophageal stratified epithelial barrier function and tight junction (TJ) proteins is not fully understood. Here, we explore the influence of acid on barrier function and TJ proteins using a newly developed model of the esophageal-like squamous epithelial cell layers that employs an air-liquid interface (ALI) system. Barrier function was determined by measuring trans-epithelial electrical resistance (TEER) and diffusion of paracellular tracers. TJ-related protein (claudin-1, claudin-4, occludin and ZO-1) expression and localization was examined by immunofluorescent staining, and by western blotting of 1% NP-40 soluble and insoluble fractions. We also examined the influence of acid (pH 2-4) on the barrier created by these cells. The in vitro ALI culture system showed a tight barrier (1500-2500 O . cm 2 ) with the expression of claudin-1, claudin-4, occludin and ZO-1 in the superficial layers. Claudin-1, claudin-4, occludin and ZO-1 were detected as dots and whisker-like lines in the superficial layers, and as a broad line in the suprabasal layers. These localization patterns are similar to those in the human esophagus. On day 7 under ALI culture, TJ proteins were detected in the superficial layers with functional properties, including decreased permeability and increased TEER. Dilated intercellular spaces were detected at the suprabasal cell layers even under the control conditions of ALI cells. pH 2 acid on the apical side significantly reduced the TEER in ALI-cultured cells. This decrease in TEER by the acid was in parallel with the decreased amount of detergent-insoluble claudin-4. Claudin-4 delocalization was confirmed by immunofluorescent staining. In conclusion, TJs are located in the superficial layers of the esophagus, and acid stimulation disrupts barrier function, at least in part by modulating the amount and localization of claudin-4 in the superficial layers.

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“…31,32 Moreover, bile salts can transiently open tight junctions to improve permeability of drug molecules or nanoparticles. 27,33 Careful handling of the isolated cornea and maintenance of its physiological activity throughout an experiment is very important for reproducibility of the results. Hydration level is a parameter frequently used to evaluate damage to the cornea.…”

mentioning

confidence: 99%

Liposomes containing bile salts as novel ocular delivery systems for tacrolimus (FK506): in vitro characterization and improved corneal permeation

Dai¹,

Zhou²,

Liu³

et al. 2013

IJN

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Abstract:The objective of this study was to investigate the potential of liposomes containing bile salts as an ophthalmic delivery system for tacrolimus to improve corneal permeability. Liposomes containing bile salts, including sodium taurocholate, sodium deoxycholate, and sodium glycocholate, were produced by the thin-film dispersion method with a particle size of approximately 100 nm and an entrapment efficiency of more than 90%. Less than 5% tacrolimus was released from conventional liposomes and from liposomes containing sodium taurocholate, sodium deoxycholate, or sodium glycocholate over 12 hours. The cellular uptake of conventional liposomes was significantly higher than that of liposomes containing bile salts. However, liposomes containing bile salts exerted a 3-4-fold increase of tacrolimus in ex vivo corneal transport of tacrolimus compared with conventional liposomes. When rabbit eyes were treated with a DiI perchlorate-loaded liposome suspension, liposomes containing bile salts showed fast and sustained penetration across the cornea. Unfortunately, liposomes containing sodium deoxycholate caused toxicity or irritation to both spontaneously derived human corneal epithelial cells and the rabbit cornea. Therefore, liposomes containing sodium taurocholate and sodium glycocholate are potential carriers in ocular drug delivery systems, given their low toxicity and vastly improved permeability.

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Acidic bile salts modulate the squamous epithelial barrier function by modulating tight junction proteins

Cited by 50 publications

References 36 publications

Gastrointestinal mucosal barrier function and diseases

Gastrointestinal mucosal barrier function and diseases

Acid modulates the squamous epithelial barrier function by modulating the localization of claudins in the superficial layers

Liposomes containing bile salts as novel ocular delivery systems for tacrolimus (FK506): in vitro characterization and improved corneal permeation

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