Kallikrein 8 Is Involved in Skin Desquamation in Cooperation with Other Kallikreins
| Autor: | Yoshio Bando, Mari Kishibe, Kazuhiko Namikawa, Ying Ping Jiang, Hidetoshi Takahashi, Hajime Iizuka, Ryuji Terayama, Shigetaka Yoshida, Yoshio Hashimoto, Daniel Perez, Akemi Ishida-Yamamoto, Branka Mitrovic |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
Keratinocytes
Hyperkeratosis Biology Biochemistry Mice KLK7 medicine Animals Humans Psoriasis Molecular Biology Cell Proliferation Mice Knockout Corneocyte integumentary system Cell adhesion molecule Desmoglein 1 Wild type Cell Differentiation Dermis Cell Biology Kallikrein medicine.disease Cell biology Disease Models Animal medicine.anatomical_structure Cancer research Tetradecanoylphorbol Acetate Kallikreins Keratinocyte KALLIKREIN 8 |
| Zdroj: | Journal of Biological Chemistry. 282:5834-5841 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.m607998200 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|