Journal Article

Caspase-14 Is Required for Filaggrin Degradation to Natural Moisturizing Factors in the Skin

Presland, Richard B., Van Damme, Petra, Caspers, Peter, Devos, Michael, Hoste, Esther, Lippens, Saskia, De Groote, Philippe, Declercq, Wim, Kezic, Sanja, Roelandt, Ria, Kemperman, Patrick, Puppels, Gerwin, Vandenabeele, Peter, Yau, Nico, Denecker, Geertrui, Takahara, Hidenari, Gevaert, Kris, Gilbert, Barbara

2011

Overview

Caspase-14 is a protease that is mainly expressed in suprabasal epidermal layers and activated during keratinocyte cornification. Caspase-14-deficient mice display reduced epidermal barrier function and increased sensitivity to UVB radiation. In these mice, profilaggrin, a protein with a pivotal role in skin barrier function, is processed correctly to its functional filaggrin (FLG) repeat unit, but proteolytic FLG fragments accumulate in the epidermis. In wild-type stratum corneum, FLG is degraded into free amino acids, some of which contribute to generation of the natural moisturizing factors (NMFs) that maintain epidermal hydration. We found that caspase-14 cleaves the FLG repeat unit and identified two caspase-14 cleavage sites. These results indicate that accumulation of FLG fragments in caspase-14-/- mice is due to a defect in the terminal FLG degradation pathway. Consequently, we show that the defective FLG degradation in caspase-14-deficient skin results in substantial reduction in the amount of NMFs, such as urocanic acid and pyrrolidone carboxylic acid. Taken together, we identified caspase-14 as a crucial protease in FLG catabolism.

• Publisher: Elsevier Inc,Nature Publishing Group,Elsevier Limited
• Subject: Amino Acid Sequence / Animals / Biological and medical sciences / Caspase 14 - deficiency / Caspase 14 - genetics / Caspase 14 - metabolism / Dermatology / Epidermis - metabolism / Female / Intermediate Filament Proteins - metabolism / Medical sciences / Mice / Mice, Knockout / Models, Animal / Proteolysis / Pyrrolidonecarboxylic Acid - metabolism / Skin - metabolism / Skin - radiation effects / Skin Physiological Phenomena / Ultraviolet Rays / Urocanic Acid - metabolism