Host defense protein S100A7/psoriasin regulates pores in the epidermis: Aquaporins and tight junctions

The most important role of the human skin is to form an effective barrier against invading microorganisms and water loss. Among the skin-derived host defense peptides (HDPs), S100A7 (psoriasin) is the principal HDP expressed in normal adult skin. We recently showed that S100A7, in addition to its antimicrobial properties, improved the skin barrier function through regulation of the expression of tight junction (TJ) proteins. Within the TJ, controlled pores exist and regulate the diffusion of water and solutes via the paracellular pathway. Aquaporins are transmembrane proteins that transport water as well as glycerol, therefore regulating water homeostasis of the epidermis. Because S100A7 enhanced function of TJ proteins, the aim of this study was to investigate whether this HDP would also regulate the expression of aquaporins in normal human keratinocytes. Compared with healthy controls, increased immunoreactivity of S100A7 was noted in both the eccrine and apocrine sweat glands from psoriasis and atopic dermatitis patients. Furthermore, we confirmed the presence of S100A7 in the sweat of normal controls. We also found that S100A7 induced the expression of several aquaporins both at the mRNA and protein levels in normal human keratinocytes. The investigation of molecular mechanism suggested that S100A7-induced expression of aquaporins was controlled by MAPK pathway, as evidenced by the inhibitory effects of MAPK specific inhibitors. In conclusion, above observations suggest that S100A7 regulates skin barrier not only through improvement of TJ function, but also enhancement of the expression of aquaporins. This provides novel evidence of the importance of S100A7 in the skin immunity.