REGULATION OF TIGHT JUNCTION PERMEABILITY BY SODIUM CAPRATE IN HUMAN KERATINOCYTES AND RECONSTRUCTED EPIDERMIS.
This study by researchers at Pola Chemical Industries Inc. and Jikei University School of Medicine used MatTek’s EpiDerm in vitro 3-D human skin tissue equivalent to investigate the effects of a known intestinal tissue tight junction dialator (sodium caprate) on human skin tissue tight junctions. Tight junctions (TJs) restrict paracellular flux of water and solutes in epithelia and endothelia. In epidermis, the physiological role of tight junctions is not fully understood. In this study, sodium caprate (C10), which dilates intestinal tight junctions, was applied to cultured human epidermal keratinocytes and reconstructed human epidermis to investigate the effects of C10 on epidermal tight junctions. C10 treatment decreased transepithelial electrical resistance and increased paracellular permeability, although Western blots showed that the expression of tight junction-related transmembrane proteins was not decreased. The effects of C10 were reversible. Immunofluorescence microscopy and immuno-replica electron microscopy showed that the localization of tight junction strands were disintegrated, concomitant with the dispersion and/or disappearance of tight junction-related molecules from the cell surface. These findings suggest that C10 impairs barrier function by physically disrupting tight junction conformation in the epidermis. Furthermore, these results also show that proper localization of the molecules on the cellular membrane is important for tight junction barrier function.
Barrier function, Claudin-1, EpiDerm, Occuludin, Paracellular flux, Paracellular permeability, Reconstructed human epidermis, Sodium caprate, Tight junction, Transepithelial electrical resistance, Transport enhancers
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