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

研究成果: Article査読

78 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)2753-2762
ページ数10
ジャーナルJournal of Investigative Dermatology
133
12
DOI
出版ステータスPublished - 12-2013

All Science Journal Classification (ASJC) codes

  • 生化学
  • 分子生物学
  • 皮膚病学
  • 細胞生物学

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