TY - JOUR
T1 - Caspase-14 is required for filaggrin degradation to natural moisturizing factors in the skin
AU - Hoste, Esther
AU - Kemperman, Patrick
AU - Devos, Michael
AU - Denecker, Geertrui
AU - Kezic, Sanja
AU - Yau, Nico
AU - Gilbert, Barbara
AU - Lippens, Saskia
AU - de Groote, Philippe
AU - Roelandt, Ria
AU - van Damme, Petra
AU - Gevaert, Kris
AU - Presland, Richard B.
AU - Takahara, Hidenari
AU - Puppels, Gerwin
AU - Caspers, Peter
AU - Vandenabeele, Peter
AU - Declercq, Wim
PY - 2011
Y1 - 2011
N2 - 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
AB - 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
U2 - https://doi.org/10.1038/jid.2011.153
DO - https://doi.org/10.1038/jid.2011.153
M3 - Article
C2 - 21654840
SN - 0022-202X
VL - 131
SP - 2233
EP - 2241
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
IS - 11
ER -