Regulation of skin pigmentation and thickness by Dickkopf 1 (DKK1).

Full Abstract

Dickkopf 1 (DKK1), an inhibitor of Wnt signaling, not only functions as a head inducer during development, but also regulates joint remodeling and bone formation, which suggests roles for DKK1 in the pathogenesis of rheumatoid arthritis and multiple myeloma. We recently demonstrated that levels of DKK1 in palmoplantar dermal fibroblasts are physiologically higher than those observed in non-palmoplantar dermal fibroblasts. Thus, the DKK1-rich mesenchyme in palmoplantar dermis affects the overlying epithelium and induces a palmoplantar phenotype in the epidermis. More specifically, DKK1 suppresses melanocyte function and growth through the regulation of microphthalmia-associated transcription factor (MITF) and beta-catenin. Furthermore, DKK1 induces the expression of keratin 9 and alpha-Kelch-like ECT2-interacting protein (alphaKLEIP) but downregulates the expression of beta-catenin, glycogen synthase kinase 3beta, protein kinase C, and proteinase-activated receptor-2 (PAR-2) in keratinocytes. Treatment of reconstructed skin with DKK1 reproduces the hypopigmentation and thickening of skin through Wnt/beta-catenin signaling. These studies elucidate why human palmoplantar skin is thicker and paler than non-palmoplantar skin through the secretion of DKK1 by fibroblasts that affect the overlying epidermis. Thus, DKK1 may be useful for reducing skin pigmentation and for thickening photo-aged skin and palmoplantar wounds caused by diabetes mellitus and rheumatic skin diseases.Journal of Investigative Dermatology Symposium Proceedings (2009) 14, 73-75; doi:10.1038/jidsymp.2009.4.

Author information

Author/s: Yamaguchi, Yuji (Y); Morita, Akimichi (A); Maeda, Akira (A); Hearing, Vincent J (VJ);

Affiliation: Department of Geriatric and Environmental Dermatology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan. yujin(-atsign-)med.nagoya-cu.ac.jp

Journal and publication information

Publication Type: Journal Article; Research Support, N.I.H., Intramural; Research Support, Non-U.S. Gov't; Review

Journal: The journal of investigative dermatology. Symposium proceedings / the Society for Investigative Dermatology, Inc. [and] European Society for Dermatological Research (J Investig Dermatol Symp Proc), published in United States. (Language: eng)

Reference: 2009-Aug; vol 14 (issue 1) : pp 73-5

Dates: Created 2009/08/13; Completed 2009/11/04;

PMID: 19675559, status: MEDLINE (last retrieval date: 11/4/2009, IMS Date: )

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