Sealing the live part of the skin: The integrated meshwork of desmosomes, tight junctions and curvilinear ridge structures in the cells of the uppermost granular layer of the human epidermis

Schlüter, Holger; Wepf, Roger; Moll, Ingrid; Franke, Werner W.

doi:10.1078/0171-9335-00434

Cited by 70 publications

(55 citation statements)

References 73 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The TJ proteins claudin-1, claudin-4, and occludin were detected as dots and whisker-like lines in the superficial layers. The TJ strand is reported to be restricted to locations where occludin is present although the function of occludin remains unclear (9,35,36,39). Therefore, we focused on claudins colocalized with occludin at junctions to analyze the functions of TJ in epithelial layers.…”

Section: Discussionmentioning

confidence: 99%

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

View full text Add to dashboard Cite

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...

show abstract

Section: Discussionmentioning

confidence: 99%

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

View full text Add to dashboard Cite

show abstract

“…7 However, more conclusive evidence of epidermal TJs in human adult skin was not established until the beginning of the millennium. [8][9][10] Almost at the same time, the notion of a functional TJ barrier in mammalian epidermis was revived by the observation that epidermal permeability barrier dysfunction developed in claudin (cldn)-1 knockout and cldn-6 transgenic mice. 11,12 Unlike the simple monolayer epithelium present in the gastrointestinal tract and bronchi where each cell expresses the full range of cellular junctions (e.g., adherens junctions, desmosomes, gap junctions, TJs), the epidermis is a highly stratified structure where cells from different layers express unique combinations of junctional complexes.…”

Section: Tight Junctions -The Under-appreciated Epidermal Barrier Strmentioning

confidence: 99%

“…Accordingly, TJ-related structures have been identified by EM below and above the SG, especially in the interdesmosomal region of various stratified epithelia. 9,17 Over the past 2 decades outstanding progress has been made in this field, but much remains to be done to fully appreciate the role epidermal TJs play in human health and disease. In this paper we will review what is known about the epidermal TJ barrier function and composition, its regulation by the immune system as well as the relevance of these observations for dermatologic diseases.…”

Section: E974451-2mentioning

confidence: 99%

Epidermal tight junctions in health and disease

et al. 2014

View full text Add to dashboard Cite

“…9 The TJ strand has been said to be restricted to wherever occludin exists, even if the function of occludin is still unclear. [23][24][25][26][27] Even in the stomach and intestine, the expression pattern of the claudins is broad, running from the apical to basolateral membrane, while that of occludin is only dense at TJs in normal tissues. 12,28 Figure 5 Influence of acid on TJ protein localization in ALI cells.…”

Section: Squamous Epithelial Barrier Function T Oshima Et Almentioning

confidence: 99%

“…This is consistent with the data from skin. 24 As the functional TJ proteins are insoluble in nonionic detergent, 10,12,29,30 in the present study, proteins from ALIcultured cells were divided into nonionic detergent (NP-40)-soluble and -insoluble fractions, and the level of claudin-1 and claudin-4 in each fraction then measured. Claudin-4 levels were lower in pH 2-stimulated cells compared with control conditions, in a time-dependent manner, suggesting that acid stimulation delocalized the claudin-4 from the TJs in the superficial layers.…”

Section: Squamous Epithelial Barrier Function T Oshima Et Almentioning

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

View full text Add to dashboard Cite

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.

show abstract

Sealing the live part of the skin: The integrated meshwork of desmosomes, tight junctions and curvilinear ridge structures in the cells of the uppermost granular layer of the human epidermis

Cited by 70 publications

References 73 publications

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

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

Epidermal tight junctions in health and disease

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

Contact Info

Product

Resources

About