Kallikrein 8 is involved in skin desquamation in cooperation with other kallikreins
Kallikrein 8 is involved in skin desquamation in cooperation with other kallikreins
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DOI：
10.1074/jbc.m607998200
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发表时间：
2007-02-23
影响因子：
4.8
通讯作者：
Yoshida, Shigetaka
中科院分区：
文献类型：
--
作者：
Kishibe, Mari;Bando, Yoshio;Yoshida, Shigetaka
激肽释放酶型丝氨酸蛋白酶，KLK 8/neuropsin，KLK 6和KLK 7，已经涉及表皮角质形成细胞的增殖和分化以及银屑病的发病机制。然而，它们在这些过程中的机械作用在很大程度上仍然未知。我们将12-O-十四烷酰基佛波醇-13-乙酸酯应用于野生型（WT）和Klk 8基因破坏的（Klk 8（-/-））小鼠皮肤，诱导类似于人类银屑病病变的角质形成细胞增殖。在WT小鼠中应用12-O-十四酰基佛波醇-13-乙酸酯后，Klk 8 mRNA以及Klk 6和Klk 7 mRNA上调。相比之下，Klk 8（-/-）小鼠显示Klk 6和Klk 7转录物、蛋白质和酶活性的最小增加。相对于WT，Klk 8（-/-）皮肤显示较少的增殖和角质层中细胞层数目的增加。然而，在敲除角质形成细胞中通过腺病毒载体过表达Klk 8并不导致Klk 6或Klk 7 mRNA的增加。Klk 8（-/-）皮肤中粘附分子DSG 1和CDSN的无效切割有助于延迟角质细胞脱落，导致角化过度表型。我们认为，在银屑病皮损中，KLK 8通过脱落角质细胞调节过度增殖并防止过度角化。
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.