Degradaton Pathway of Filaggrin

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  • フィラグリンの分解系はどうなっているのか？

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Filaggrin is completely degraded to produce natural moisturizing factors (NMF), which is essential for maintenance of skin hydration. We investigated the degradation pathway and identified bleomycin hydrolase (BH) as an NMF-generating enzyme. Further analyses revealed that filaggrin is first degraded by caspase-14, followed by calpain I digestion, and finally degraded into free amino acids by BH. We found that BH activity was significantly down-regulated in the corneocyte extract from skins with sixties compared to those with forties. Contents of free amino acids also showed significant decrease in the extract of sixties. Deletion study identified a critical region for BH promoter activity within -216 bp. This region included SP1, MZF1 and IRF1/2 recognition sequences, indicating that the BH transcription would be regulated both with differentiation and inflammation. Lastly we examined expression of BH in atopic dermatitis (AD). BH activity and expression markedly decreased both in the lesional and non-lesional skin with AD, suggesting that defects in the filaggrin degradation pathway would play a role in the pathogenesis of AD. Skin Research, Suppl.　16: 21-24, 2011

Journal

  • Hifu no kagaku

    Hifu no kagaku 10 (Suppl.16), 21-24, 2011

    Meeting of Osaka Dermatological Association/Meeting of Keiji Dermatological Association

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