title: 12-O-tetradecanoylphorbol-13-acetate activates hair follicle melanocytes for hair pigmentation via Wnt/β-catenin signaling.
abstract: Melanocyte stem cells (McSCs) undergo cyclical activation and quiescence together with hair follicle stem cells (HFSCs). This process is strictly controlled by the autonomous and extrinsic signaling environment. However, the modulation of factors important for the activation of McSCs for hair pigmentation remains unclear. 12-O-tetradecanoylphorbol-13-acetate (TPA) mimics vital signaling pathways involved in melanocyte growth and melanogenesis in vitro. To investigate whether TPA regulates quiescent McSCs for hair pigmentation, we topically smeared TPA on 7-week-old mouse dorsal skin and found that TPA stimulated hair growth and hair matrix pigmentation. These changes were associated with a significant increase in the number of hair bulb melanocytes. Moreover, in the TPA-treated group, hair bulge McSCs and hair bulb melanoblasts actively proliferated. At the molecular level, nuclear β-catenin, a key factor of Wnt/β-catenin signaling, was highly synthesized in melanocytes and keratinocytes in TPA-induced hair bulbs. Inhibition of Wnt/β-catenin signaling by injecting Dickkopf1 plasmids into TPA-treated skin decreased hair matrix pigmentation and inhibited the proliferation and differentiation of McSCs. Our findings suggest that the topical application of TPA stimulates the proliferation and differentiation of McSCs and their progeny for hair matrix pigmentation by activating Wnt/β-catenin signaling. This might provide a useful experimental model for the study of signals controlling the activation of McSCs.
authors.affiliation: Department of Dermatology, Daping Hospital, The Third Military Medical University, Chongqing, 400038, China.|Department of Dermatology, Wuhan General Hospital of Guangzhou Military Area Command, Wuhan, 430070, China.
authors.forename: Weiming
authors.initials: W
authors.lastname: Qiu
authors.affiliation: Department of Dermatology, Daping Hospital, The Third Military Medical University, Chongqing, 400038, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Tang
authors.affiliation: Department of Cell Biology, The Third Military Medical University, Chongqing, 400038, China.
authors.forename: Haiying
authors.initials: H
authors.lastname: Guo
authors.affiliation: "111" Project Laboratory of Biomechanics and Tissue Repair, College of Bioengineering, Chongqing University, Chongqing, 400044, China.
authors.forename: Mingxing
authors.initials: M
authors.lastname: Lei
authors.affiliation: Department of Dermatology, Daping Hospital, The Third Military Medical University, Chongqing, 400038, China.
authors.forename: Hongtao
authors.initials: H
authors.lastname: Yan
authors.affiliation: Department of Cell Biology, The Third Military Medical University, Chongqing, 400038, China. 129hx@163.com.
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Lian
authors.affiliation: Department of Dermatology, Daping Hospital, The Third Military Medical University, Chongqing, 400038, China. wjjjj@163.com.
authors.forename: Jinjin
authors.initials: J
authors.lastname: Wu
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D018859:Hair Follicle / Q000166:cytology* / Q000254:growth & development; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects; D008544:Melanocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D010858:Pigmentation / Q000187:drug effects*; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D060449:Wnt Signaling Pathway / Q000187:drug effects*
chemical_list: C501127:Dkk1 protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; D013755:Tetradecanoylphorbol Acetate
keywords: 12-O-tetradecanoylphorbol-13-acetate; Dickkopf1; Hair pigmentation; Melanocyte stem cell; β-Catenin