Dickkopf 1 (DKK1) is an inhibitor of Wnt signaling. It functions as a head inducer during development and also regulates joint remodeling and bone formation, which suggests roles for DKK1 in the pathogenesis of rheumatoid arthritis and multiple myeloma. 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.
DKK1 suppresses melanocyte function and growth through the regulation of microphthalmia-associated transcription factor (MITF) and -catenin.
DKK1 induces the expression of keratin 9 and -Kelch-like ECT2-interacting protein (KLEIP) but downregulates the expression of -catenin, glycogen synthase kinase 3, 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/-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.
For review and figure :
Yamaguchi Y, Morita A, Maeda A, Hearing VJ. Regulation of skin pigmentation and thickness by Dickkopf 1 (DKK1). J Investig Dermatol Symp Proc. 2009 Aug ;14(1):73-5. Review. PubMed PMID : 19675559 ; PubMed Central PMCID : PMC2793095.