Skin presenting a higher level of caspase‐14 is better protected from UVB irradiation according to in vitro and in vivo studies

Summary Caspase‐14, a cysteine endoproteinase belonging to the conserved family of aspartate‐specific proteinases, was shown to play an important role in the terminal differentiation of keratinocytes and barrier function of the skin. In the present study, we developed a biofunctional compound that we described as a modulator of caspase‐14 expression. Using normal human keratinocytes (NHK) in culture and human skin biopsies, this compound was shown to increase caspase‐14 expression and partially reverse the effect of caspase‐14‐specific siRNA on NHK. Moreover, the increase in filaggrin expression visualized on skin biopsies and the recovery of the barrier structure after tape‐stripping indicated that this compound could exhibit a beneficial effect on the skin barrier function. Considering the possible link between caspase‐14 and the barrier function, a UVB irradiation on NHK and skin biopsies previously treated with the caspase‐14 inducer, was performed. Results indicated that pretreated skin biopsies exhibited less signs of UV damage such as active caspase‐3 and cyclobutane pyrimidine dimers (CPDs). Likewise, pretreated NHK were protected from UV‐induced genomic DNA damage, as revealed by the Comet Assay. Finally, a clinical test showed a reduction of transepidermal water loss (TEWL) on the treated skin compared with placebo, under UV stress condition, confirming a protecting effect. Taken together, these results strongly suggest that, by increasing caspase‐14 expression, the biofunctional compound could exhibit a protective effect on the skin barrier function, especially in case of barrier damage and UV irradiation.