Organic osmolytes increase expression of specific tight junction proteins in skin and alter barrier function in keratinocytes

Background The epidermal barrier is important for water conservation, failure of which is evident in dry-skin conditions. Barrier function is fulfilled by the stratum corneum, tight junctions (TJs, which control extracellular water) and keratinocyte mechanisms, such as organic osmolyte transport, which regulate intracellular water homeostasis. Organic osmolyte transport by keratinocytes is largely unexplored and nothing is known regarding how cellular and extracellular mechanisms of water conservation may interact. Objectives We aimed to characterize osmolyte transporters in skin and keratinocytes, and, using transporter inhibitors, to investigate whether osmolytes can modifyTJs. Such modification would suggest a possible link between intracellular and extracellular mechanisms of water regulation in skin. Methods Immunostaining and quantitative polymerase chain reaction of organic osmolyte-treated organ-cultured skin were used to identify changes to organic osmolyte transporters, andTJprotein and gene expression.TJfunctional assays were performed on organic osmolyte-treated primary human keratinocytes in culture. Results Immunostaining demonstrated the expression of transporters for betaine, taurine andmyo-inositol in transporter-specific patterns. Treatment of human skin with either betaine or taurine increased the expression of claudin-1, claudin-4 and occludin. Osmolyte transporter inhibition abolished this response. Betaine and taurine increasedTJfunction in primary human keratinocytesin vitro. Conclusions Treatment of skin with organic osmolytes modulatesTJstructure and function, which could contribute to the epidermal barrier. This emphasizes a role for organic osmolytes beyond the maintenance of intracellular osmolarity. This could be harnessed to enhance topical therapies for diseases characterized by skin barrier dysfunction.

Automated summary

Research has identified the presence of organic osmolyte transporters in skin and keratinocytes, and shown that treatment with organic osmolytes can modify tight junction structure and function, potentially contributing to the epidermal barrier. This suggests a potential link between intracellular and extracellular mechanisms of water regulation in skin.