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Epidermal barrier function is provided by the highly keratinised stratum corneum and also by tight junctions (TJs) in the granular layer of skin. The development of the TJ barrier significantly deteriorates in response to ultraviolet B radiation (UVB). Following exposure to UVB, keratinocytes accumulate organic osmolytes, which are known to preserve cell volume during water stress. Since TJs are intimately associated with control of water homeostasis in skin, we hypothesised that there may be a direct influence of osmolytes on TJ development. Exposure of rat epidermal keratinocytes (REKs) to a single dose of UVB reduced the function of developing TJs. This was concomitant with dislocalisation of claudin-1 and claudin-4 from the keratinocyte plasma membrane, phosphorylation of occludin and elevation of reactive oxygen species (ROS). In the presence of organic osmolytes, these effects were negated but were independent of the effects of these molecules on cell volume, elevation of ROS or the gene expression of TJ proteins. These data suggest that organic osmolytes affect TJs via post-translational mechanism(s) possibly involving protection of the native conformation of TJ proteins.

The skin is known to be the largest organ in human organism creating interface with outer environment. The skin provides protective barrier against pathogens, physical and chemical insults, and against uncontrolled loss of water. The barrier function was primarily attributed to the stratum corneum (SC) but recent studies confirmed that epidermal tight junctions (TJs) also play important role in maintaining barrier properties of the skin. Independent observations indicate that barrier function and its recovery is impaired in aged skin. However, trans-epidermal water loss (TEWL) values remains rather unchanged in elderly population. UV radiation as major factor of photoageing impairs TJ proteins, but TJs have great self-regenerative potential. Since it may be possible that TJs can compensate TEWL in elderly due to its regenerative and compensatory capabilities, important question remains to be answered: how are TJs regulated during skin ageing? This review provides an insight into TJs functioning as epidermal barrier and summarizes current knowledge about the impact of ageing on the barrier function of the skin and epidermal TJs., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Dietary glucosylceramide increased the expression of claudin-1 in UVB-irradiated mouse epidermis. Sphingosine and phytosphingosine, metabolites of glucosylceramide, increased trans-epithelial electrical resistance, and phytosphingosine increased claudin-1 mRNA expression in cultured keratinocytes. Our results indicate that the skin barrier improvement induced by dietary glucosylceramide might be due to enhancement of tight junction function, mediated by increased expression of claudin-1 induced by sphingoid metabolites.

It has not been confirmed whether tight junctions (TJs) function as a paracellular permeability barrier in adult human skin. To clarify this issue, we performed a TJ permeability assay using human skin obtained from abdominal plastic surgery. Occludin, a marker protein of TJs, was expressed in the granular layer, in which a subcutaneously injected paracellular tracer, Sulfo-NHS-LC-Biotin (556.59 Da), was halted. Incubation with ochratoxin A decreased the expression of claudin-4, an integral membrane protein of TJs, and the diffusion of paracellular tracer was no longer prevented at the TJs. These results demonstrate that human epidermis possesses TJs that function as an intercellular permeability barrier at least against small molecules (∼550 Da). UVB irradiation of human skin xenografts and human skin equivalents (HSEs) resulted in functional deterioration of TJs. Immunocytochemical staining of cultured keratinocytes showed that occludin was localized into dot-like shapes and formed a discontinuous network when exposed to UVB irradiation. Furthermore, UVB irradiation downregulated the active forms of Rac1 and atypical protein kinase C, suggesting that their inactivation caused functional deterioration of TJs. In conclusion, TJs function as a paracellular barrier against small molecules (∼550 Da) in human epidermis and are functionally deteriorated by UVB irradiation.

In epithelia, tight junctions (TJs) create a primary barrier to the diffusion of solutes through the paracellular pathway. Although TJ-related molecules are present in the epidermis, the precise mechanisms underlying TJ functions in this tissue remain unclear. In this study, we use an ultraviolet (UV) B-irradiated murine skin model, in which the epidermal barrier function has been perturbed, to demonstrate a correlation between the expression patterns of TJ-related molecules and the epidermal permeability of TJs. Occludin remained localized in the upper epidermis, regardless of UVB irradiation (0.15 J per cm(2)). ZO-1 was localized in the upper portion of normal epidermis, and within 3-4 days of UVB irradiation, it was expressed throughout the upper epidermis and their expression coincided with epidermal thickening. Protein expression of claudin-1 and occludin did not alter until 3 and 4 days after UVB irradiation, respectively and thereafter expression remained elevated above pre-irradiation levels. An in vivo epidermal permeability assay revealed that tight junction-barrier function was perturbed by UVB irradiation, whereby biotinylated markers clearly permeated the stratum granulosum 3-5 days after irradiation. These results suggest that TJ-related molecules play important roles in epidermal barrier function in murine skin and show that changes in their expression patterns are associated with epidermal barrier perturbation after UVB irradiation. Specifically, it appears that epidermal barrier recovery is accelerated by the increased production and dense localization of occludin in the cell-cell contact region of the stratum granulosum.