The Ronald O. Perelman Department of Dermatology, New York University School of Medicine, New York, New York, USA; The Department of Cell Biology, New York University School of Medicine, New York, New York, USA.
Department of Pharmacology, Kyoto University, Sakyo, Kyoto, Japan.
J Invest Dermatol. 2018 Jul;138(7):1591-1600. doi: 10.1016/j.jid.2018.01.030. Epub 2018 Feb 8.
Abnormal pigmentation is commonly seen in the wound scar. Despite advancements in the research of wound healing, little is known about the repopulation of melanocytes in the healed skin. Previous studies have shown the capacity of melanocyte stem cells in the hair follicle to contribute skin epidermal melanocytes after injury in mice and humans. Here, we focused on the Wnt pathway, known to be a vital regulator of melanocyte stem cells in efforts to better understand the regulation of follicle-derived epidermal melanocytes during wound healing. We showed that transgenic expression of Wnt inhibitor Dkk1 in melanocytes reduced epidermal melanocytes in the wound scar. Conversely, forced activation of Wnt signaling by genetically stabilizing β-catenin in melanocytes increases epidermal melanocytes. Furthermore, we show that deletion of Wntless (Wls), a gene required for Wnt ligand secretion, within epithelial cells results in failure in activating Wnt signaling in adjacent epidermal melanocytes. These results show the essential function of extrinsic Wnt ligands in initiating Wnt signaling in follicle-derived epidermal melanocytes during wound healing. Collectively, our results suggest the potential for Wnt signal regulation to promote melanocyte regeneration and provide a potential molecular window to promote proper melanocyte regeneration after wounding and in conditions such as vitiligo.
伤口疤痕中通常可见异常色素沉着。尽管在伤口愈合研究方面取得了进展，但对于愈合皮肤中黑素细胞的再增殖知之甚少。先前的研究表明，毛囊中的黑素细胞干细胞在小鼠和人类受伤后能够为皮肤表皮黑素细胞提供贡献。在这里，我们专注于 Wnt 途径，已知其是黑素细胞干细胞的重要调节剂，旨在更好地了解伤口愈合过程中毛囊衍生的表皮黑素细胞的调节。我们表明，在黑素细胞中转基因表达 Wnt 抑制剂 Dkk1 会减少伤口疤痕中的表皮黑素细胞。相反，通过在黑素细胞中遗传稳定 β-连环蛋白来强制激活 Wnt 信号会增加表皮黑素细胞。此外，我们表明，上皮细胞中 Wnt 配体分泌所必需的基因 Wntless (Wls) 的缺失会导致相邻表皮黑素细胞中无法激活 Wnt 信号。这些结果表明，外在 Wnt 配体在启动伤口愈合过程中毛囊衍生的表皮黑素细胞中的 Wnt 信号中具有重要功能。总的来说，我们的研究结果表明，Wnt 信号调节有可能促进黑素细胞再生，并为创伤后和白癜风等情况下适当的黑素细胞再生提供潜在的分子窗口。
