Format

Send to

Choose Destination
Br J Dermatol. 2010 Sep;163(3):466-75. doi: 10.1111/j.1365-2133.2010.09864.x. Epub 2010 Aug 12.

Molecular mechanism of kallikrein-related peptidase 8/neuropsin-induced hyperkeratosis in inflamed skin.

Author information

1
Department of Anatomy and Neuroscience, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan. kensngk@anat2.med.osaka-u.ac.jp

Abstract

BACKGROUND:

Hyperkeratosis and acanthosis occur in inflamed skin. Proliferation and differentiation of keratinocytes are important processes during epidermal repair after inflammation. Neuropsin and its human homologue kallikrein-related peptidase 8 (KLK8) have been reported to be involved in epidermal proliferation and differentiation, but the involved molecular mechanisms are obscure.

OBJECTIVES:

To explore the molecular mechanism of KLK8/neuropsin-induced hyperkeratosis and acanthosis in inflamed skin.

METHODS:

The molecular mechanism involved in KLK8/neuropsin-induced hyperkeratosis and acanthosis in inflamed skin was investigated both in vivo and in vitro using neuropsin knockout mice and KLK8 knockdown human keratinocytes. Neuropsin-related genes were identified by differential gene display. The localization and functional relationship of the molecules affected downstream of KLK8/neuropsin in normal and inflamed skin were analysed by in situ hybridization and immunohistochemistry.

RESULTS:

  Hyperkeratosis and acanthosis in sodium lauryl sulphate-stimulated skin were markedly inhibited in neuropsin knockout mice. Knockdown of KLK8/neuropsin increased transcription factor activator protein-2α (AP-2α) expression and decreased keratin 10 expression in human keratinocytes and mouse skin, respectively. AP-2α has been reported to inhibit epidermal proliferation and keratin 10 expression. Distributional analysis showed that KLK8/neuropsin was expressed in the stratum spinosum, AP-2α was expressed in the stratum basale and the lower part of the stratum spinosum, and keratin 10 was expressed throughout the stratum spinosum.

CONCLUSIONS:

The above findings suggest the following mechanism of events underlying KLK8/neuropsin-induced hyperkeratosis: (i) skin inflammation increases KLK8/neuropsin expression in the stratum spinosum; (ii) the released KLK8/neuropsin inhibits AP-2α expression in the cells of the stratum basale and stratum spinosum; (iii) the decrease in AP-2α results in cell proliferation in the stratum basale and cell differentiation in the stratum spinosum, with an increase in keratin 10 expression.

[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Wiley
Loading ...
Support Center