SASPase regulates stratum corneum hydration through profilaggrin-to-filaggrin processing

Takeshi Matsui, Kenichi Miyamoto, Akiharu Kubo, Hiroshi Kawasaki, Tamotsu Ebihara, Kazuya Hata, Shinya Tanahashi, Shizuko Ichinose, Issei Imoto, Johji Inazawa, Jun Kudo, Masayuki Amagai

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Abstract

The stratum corneum (SC), the outermost layer of the epidermis, acts as a barrier against the external environment. It is hydrated by endogenous humectants to avoid desiccation. However, the molecular mechanisms of SC hydration remain unclear. We report that skin-specific retroviral-like aspartic protease (SASPase) deficiency in hairless mice resulted in dry skin and a thicker and less hydrated SC with an accumulation of aberrantly processed profilaggrin, a marked decrease of filaggrin, but no alteration in free amino acid composition, compared with control hairless mice. We demonstrated that recombinant SASPase directly cleaved a linker peptide of recombinant profilaggrin. Furthermore, missense mutations were detected in 5 of 196 atopic dermatitis (AD) patients and 2 of 28 normal individuals. Among these, the V243A mutation induced complete absence of protease activity in vitro, while the V187I mutation induced a marked decrease in its activity. These findings indicate that SASPase activity is indispensable for processing profilaggrin and maintaining the texture and hydration of the SC. This provides a novel approach for elucidating the complex pathophysiology of atopic dry skin.

Original languageEnglish
Pages (from-to)320-333
Number of pages14
JournalEMBO Molecular Medicine
Volume3
Issue number6
DOIs
Publication statusPublished - 2011 Jun

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Keywords

  • Dermatology
  • Epidermis
  • Filaggrin
  • Protease
  • Skin

ASJC Scopus subject areas

  • Molecular Medicine

Cite this

Matsui, T., Miyamoto, K., Kubo, A., Kawasaki, H., Ebihara, T., Hata, K., Tanahashi, S., Ichinose, S., Imoto, I., Inazawa, J., Kudo, J., & Amagai, M. (2011). SASPase regulates stratum corneum hydration through profilaggrin-to-filaggrin processing. EMBO Molecular Medicine, 3(6), 320-333. https://doi.org/10.1002/emmm.201100140