Journal
JOURNAL OF INVESTIGATIVE DERMATOLOGY
Volume 131, Issue 11, Pages 2233-2241Publisher
ELSEVIER SCIENCE INC
DOI: 10.1038/jid.2011.153
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Funding
- Flanders Institute for Biotechnology (VIB), Ghent University
- FP6 Integrated Project [LSHB-CT-2005-019067]
- COST [BM0903]
- Inter-university Attraction Poles, IAP [6/18]
- Fonds Wetenschappelijke Onderzoek Vlaanderen [3G.0218.06, G.0226.09, 1.5.169.08]
- Ghent University [BOF-GOA-12.0505.02.E]
- IWT-Vlaanderen
- Flemish Government
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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.
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