Wnt/β-Catenin and kit signaling sequentially regulate melanocyte stem cell differentiation in uvb-induced epidermal pigmentation

Takaaki Yamada, Seiji Hasegawa, Yu Inoue, Yasushi Date, Naoki Yamamoto, Hiroshi Mizutani, Satoru Nakata, Kayoko Matsunaga, Hirohiko Akamatsu

Research output: Contribution to journalArticlepeer-review

70 Citations (Scopus)

Abstract

UV radiation is a well-known inducer of epidermal pigmentation that is utilized in therapy for vitiligo, one of the skin depigmentation disorders. Although it has been reported that melanocyte stem cells (McSCs) play essential roles in hair pigmentation, the relationship between McSCs and epidermal pigmentation remains unclear. Repetitive UVB irradiation on the dorsal skin of F1 mice of HR-1 × HR/De caused apparent epidermal pigmentation, and it was characterized by increase in the number of melanocytes. Interestingly, differentiation of McSCs into melanoblasts in hair follicles was followed by induction of epidermal melanocyte differentiation. Administration of a neutralizing antibody for Kit receptor that depletes resident melanoblasts could not suppress increased number of melanocytes. UVB irradiation also induced robust expression of Wnt7a as well as Kitl in epidermis, and β-catenin translocation into nucleus in McSCs. Intradermal injection of IWR-1 (inhibitor of Wnt response 1), a chemical inhibitor of β-catenin activation, and small interfering RNA (siRNA) against Wnt7a suppressed increase in the number of epidermal melanocytes. Taken altogether, it was demonstrated that Wnt7a triggered McSCs differentiation through β-catenin activation, and Kitl might induce following migration of melanoblasts to epidermis. These findings will help in developing therapeutic technologies for vitiligo and other pigmentary disorders.

Original languageEnglish
Pages (from-to)2753-2762
Number of pages10
JournalJournal of Investigative Dermatology
Volume133
Issue number12
DOIs
Publication statusPublished - 12-2013

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

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