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Accelerated differentiation of melanocyte stem cells contributes to the formation of hyperpigmented maculae
Author(s) -
Yamada Takaaki,
Hasegawa Seiji,
Inoue Yu,
Date Yasushi,
Arima Masaru,
Yagami Akiko,
Iwata Yohei,
Takahashi Masayuki,
Yamamoto Naoki,
Mizutani Hiroshi,
Nakata Satoru,
Matsunaga Kayoko,
Akamatsu Hirohiko
Publication year - 2014
Publication title -
experimental dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.108
H-Index - 96
eISSN - 1600-0625
pISSN - 0906-6705
DOI - 10.1111/exd.12496
Subject(s) - stem cell , melanocyte , wnt signaling pathway , biology , microbiology and biotechnology , cellular differentiation , cancer research , pathology , immunology , signal transduction , melanoma , medicine , genetics , gene
It has been reported that the abnormal regulation of melanocyte stem cells (Mc SC s) causes hair greying; however, little is known about the role of Mc SC s in skin hyperpigmentation such as solar lentigines ( SL s). To investigate the involvement of Mc SC s in SL s, the canonical Wnt signalling pathway that triggers the differentiation of Mc SC s was analysed in UVB ‐induced delayed hyperpigmented maculae in mice and human SL lesions. After inducing hyperpigmented maculae on dorsal skin of F1 mice of HR ‐1× HR /De, which was formed long after repeated UVB irradiation, the epidermal Wnt1 expression and the number of nuclear β‐catenin‐positive Mc SC s were increased as compared to non‐irradiated control mice. Furthermore, the expression of dopachrome tautomerase (Dct), a downstream target of β‐catenin, was significantly upregulated in Mc SC s of UVB ‐irradiated mice. The Wnt1 expression and the number of nuclear β‐catenin‐positive Mc SC s were also higher in human SL lesions than in normal skin. Recombinant Wnt1 protein induced melanocyte‐related genes including Dct in early‐passage normal human melanocytes ( NHEM s), an in vitro Mc SC model. These results demonstrate that the canonical Wnt signalling pathway is activated in SL lesions and strongly suggest that the accelerated differentiation of Mc SC s is involved in SL pathogenesis.