title: Wnt/β-catenin and kit signaling sequentially regulate melanocyte stem cell differentiation in UVB-induced epidermal pigmentation.
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.
authors.affiliation: Research Laboratories, Nippon Menard Cosmetic, Nagoya, Japan; Department of Dermatology, Fujita Health University School of Medicine, Toyoake, Japan. Electronic address: yamada.takaaki@menard.co.jp.
authors.forename: Takaaki
authors.initials: T
authors.lastname: Yamada
authors.affiliation: Research Laboratories, Nippon Menard Cosmetic, Nagoya, Japan; Department of Dermatology, Fujita Health University School of Medicine, Toyoake, Japan.
authors.forename: Seiji
authors.initials: S
authors.lastname: Hasegawa
authors.affiliation: Research Laboratories, Nippon Menard Cosmetic, Nagoya, Japan.
authors.forename: Yu
authors.initials: Y
authors.lastname: Inoue
authors.affiliation: Research Laboratories, Nippon Menard Cosmetic, Nagoya, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Date
authors.affiliation: Laboratory of Molecular Biology and Histochemistry, Fujita Health University Joint Research Laboratory, Toyoake, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Yamamoto
authors.affiliation: Research Laboratories, Nippon Menard Cosmetic, Nagoya, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Mizutani
authors.affiliation: Research Laboratories, Nippon Menard Cosmetic, Nagoya, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Nakata
authors.affiliation: Department of Dermatology, Fujita Health University School of Medicine, Toyoake, Japan.
authors.forename: Kayoko
authors.initials: K
authors.lastname: Matsunaga
authors.affiliation: Department of Applied Cell and Regenerative Medicine, Fujita Health University School of Medicine, Toyoake, Japan.
authors.forename: Hirohiko
authors.initials: H
authors.lastname: Akamatsu
mesh_terms: D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D004817:Epidermis / Q000378:metabolism*; D005786:Gene Expression Regulation; D018859:Hair Follicle / Q000378:metabolism; D006801:Humans; D015603:Keratinocytes / Q000166:cytology; D008544:Melanocytes / Q000166:cytology*; D051379:Mice; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism; D012880:Skin Pigmentation; D019089:Stem Cell Factor / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology / Q000528:radiation effects; D014466:Ultraviolet Rays; D051153:Wnt Proteins / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism*
chemical_list: C495267:CTNNB1 protein, mouse; D034741:RNA, Small Interfering; D019089:Stem Cell Factor; C092778:WNT7A protein, human; D051153:Wnt Proteins; C490508:Wnt7a protein, mouse; D051176:beta Catenin; D019009:Proto-Oncogene Proteins c-kit