Qiu Weiming, Tang Hui, Guo Haiying, Lei Mingxing, Yan Hongtao, Lian Xiaohua, Wu Jinjin
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.
Cell Tissue Res. 2016 Nov;366(2):329-340. doi: 10.1007/s00441-016-2450-6. Epub 2016 Jul 27.
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.
黑素细胞干细胞（McSCs）与毛囊干细胞（HFSCs）一起经历周期性激活和静止。这一过程受到自主和外在信号环境的严格控制。然而，对于毛发色素沉着中McSCs激活的重要因素的调节仍不清楚。十四酰佛波醇-13-乙酸酯（TPA）在体外模拟参与黑素细胞生长和黑素生成的重要信号通路。为了研究TPA是否调节静止的McSCs以促进毛发色素沉着，我们将TPA局部涂抹在7周龄小鼠的背部皮肤上，发现TPA刺激了毛发生长和毛基质色素沉着。这些变化与毛球黑素细胞数量的显著增加有关。此外，在TPA处理组中，毛囊隆突部的McSCs和毛球黑素母细胞积极增殖。在分子水平上，核β-连环蛋白是Wnt/β-连环蛋白信号通路的关键因子，在TPA诱导的毛球中的黑素细胞和角质形成细胞中高度合成。通过向TPA处理的皮肤中注射Dickkopf1质粒抑制Wnt/β-连环蛋白信号通路，可减少毛基质色素沉着，并抑制McSCs的增殖和分化。我们的研究结果表明，局部应用TPA通过激活Wnt/β-连环蛋白信号通路刺激McSCs及其后代的增殖和分化，以促进毛基质色素沉着。这可能为研究控制McSCs激活的信号提供一个有用的实验模型。
