Kallikrein 8 is involved in skin desquamation in cooperation with other kallikreins.
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.
Kishibe
Mari
M
Departments of Structural Anatomy and Neuroscience and Dermatology, Asahikawa Medical College, Midorigaoka-Higashi 2-1-1-1, Asahikawa 078-8510, Japan.
Bando
Yoshio
Y
Terayama
Ryuji
R
Namikawa
Kazuhiko
K
Takahashi
Hidetoshi
H
Hashimoto
Yoshio
Y
Ishida-Yamamoto
Akemi
A
Jiang
Ying-Ping
YP
Mitrovic
Branka
B
Perez
Daniel
D
Iizuka
Hajime
H
Yoshida
Shigetaka
S
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects; D020405:Dermis / Q000201:enzymology* / Q000473:pathology; D051183:Desmoglein 1 / Q000378:metabolism; D004195:Disease Models, Animal; D006801:Humans; D007610:Kallikreins / Q000172:deficiency / Q000378:metabolism*; D015603:Keratinocytes / Q000201:enzymology* / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D011565:Psoriasis / Q000139:chemically induced / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D013755:Tetradecanoylphorbol Acetate / Q000031:analogs & derivatives / Q000633:toxicity
D051183:Desmoglein 1; C020922:4-O-methyl-12-O-tetradecanoylphorbol 13-acetate; D007610:Kallikreins; C114664:Prss19 protein, mouse; D013755:Tetradecanoylphorbol Acetate