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

Research output: Contribution to journalArticle

52 Citations (Scopus)

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

Fingerprint

Cornea
Peptide Hydrolases
Hairless Mouse
Skin
Hygroscopic Agents
Desiccation
Mutation
Missense Mutation
Epidermis
Amino Acids
Peptides
filaggrin

Keywords

  • Dermatology
  • Epidermis
  • Filaggrin
  • Protease
  • Skin

ASJC Scopus subject areas

  • Molecular Medicine

Cite this

SASPase regulates stratum corneum hydration through profilaggrin-to-filaggrin processing. / Matsui, Takeshi; Miyamoto, Kenichi; Kubo, Akiharu; Kawasaki, Hiroshi; Ebihara, Tamotsu; Hata, Kazuya; Tanahashi, Shinya; Ichinose, Shizuko; Imoto, Issei; Inazawa, Johji; Kudo, Jun; Amagai, Masayuki.

In: EMBO Molecular Medicine, Vol. 3, No. 6, 06.2011, p. 320-333.

Research output: Contribution to journalArticle

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, vol. 3, no. 6, pp. 320-333. https://doi.org/10.1002/emmm.201100140
Matsui, Takeshi ; Miyamoto, Kenichi ; Kubo, Akiharu ; Kawasaki, Hiroshi ; Ebihara, Tamotsu ; Hata, Kazuya ; Tanahashi, Shinya ; Ichinose, Shizuko ; Imoto, Issei ; Inazawa, Johji ; Kudo, Jun ; Amagai, Masayuki. / SASPase regulates stratum corneum hydration through profilaggrin-to-filaggrin processing. In: EMBO Molecular Medicine. 2011 ; Vol. 3, No. 6. pp. 320-333.
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