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

E Hoste, P Kemperman, M Devos, G Denecker, S Kezic, N Yau, B Gilbert, S Lippens, P De Groote, R Roelandt, P van Damme, K Gevaert, RB Presland, H Takahara, Gerwin Puppels, Peter Caspers, P Vandenabeele, W Declercq

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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.
Original languageUndefined/Unknown
Pages (from-to)2233-2241
Number of pages9
JournalJournal of Investigative Dermatology
Issue number11
Publication statusPublished - 2011

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  • EMC MM-03-61-05-A

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