Kallikrein 8 is involved in skin desquamation in cooperation with other kallikreins

Mari Kishibe, Yoshio Bando, Ryuji Terayama, Kazuhiko Namikawa, Hidetoshi Takahashi, Yoshio Hashimoto, Akemi Ishida-Yamamoto, Ying Ping Jiang, Branka Mitrovic, Daniel Perez, Hajime Iizuka, Shigetaka Yoshida

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

Kallikrein type serine proteases, KLK8/neuropsin, KLK6, and KLK7, have been implicated in the proliferation and differentiation of epidermal keratinocytes and in the pathogenesis of psoriasis. However, their mechanistic roles in these processes remain largely unknown. We applied 12-O-tetradecanoylphorbol-13- acetate on the wild type (WT) and the Klk8 gene-disrupted (Klk8-/-) mouse skin, inducing keratinocyte proliferation similar to the human psoriatic lesion. Klk8 mRNA as well as Klk6 and Klk7 mRNA were up-regulated after 12-O-tetradecanoylphorbol-13-acetate application in the WT mice. In contrast, Klk8-/- mice showed minimum increases of Klk6 and Klk7 transcripts, the proteins, and enzymatic activities. Relative to the WT, the Klk8 -/- skin showed less proliferation and an increase in the number of cell layers in the stratum corneum. However, overexpression of Klk8 by adenovirus vector in knock-out keratinocytes did not result in an increase in Klk6 or Klk7 mRNA. The inefficient cleavage of adhesion molecules DSG1 and CDSN in Klk8-/- skin contributes to a delay in corneocyte shedding, resulting in the hyperkeratosis phenotype. We propose that in psoriatic lesion, KLK8 modulates hyperproliferation and prevents excessive hyperkeratosis by shedding the corneocytes.

Original languageEnglish
Pages (from-to)5834-5841
Number of pages8
JournalJournal of Biological Chemistry
Volume282
Issue number8
DOIs
Publication statusPublished - Feb 23 2007

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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  • Cite this

    Kishibe, M., Bando, Y., Terayama, R., Namikawa, K., Takahashi, H., Hashimoto, Y., Ishida-Yamamoto, A., Jiang, Y. P., Mitrovic, B., Perez, D., Iizuka, H., & Yoshida, S. (2007). Kallikrein 8 is involved in skin desquamation in cooperation with other kallikreins. Journal of Biological Chemistry, 282(8), 5834-5841. https://doi.org/10.1074/jbc.M607998200