Smith Andrew A, Li Jingtao, Liu Bo, Hunter Daniel, Pyles Malcolm, Gillette Martin, Dhamdhere Girija R, Abo Arie, Oro Anthony, Helms Jill A
Division of Plastic and Reconstructive Surgery, Department of Surgery, Stanford School of Medicine, Stanford University, Stanford, California, USA.
Division of Plastic and Reconstructive Surgery, Department of Surgery, Stanford School of Medicine, Stanford University, Stanford, California, USA; Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Wuhou, Chengdu, Sichuan, China.
J Invest Dermatol. 2016 Aug;136(8):1549-1558. doi: 10.1016/j.jid.2016.01.041. Epub 2016 Apr 22.
Wnt signaling is required for the development of the hair follicle, and for inciting the growth (anagen) phase of the hair cycle. Most strategies to enhance Wnt signaling for hair growth create a state of constitutive Wnt activation, which leads to neoplastic transformation of the epithelial hair matrix. Using Axin2(LacZ/+) and Axin2(Cre/+)R26R(mTmG/+) reporter mice and RNA analyses, we show that Wnt signaling is elevated during anagen, is reduced at the onset of catagen, and can be reamplified in the skin and surrounding hair follicles via intradermal injection of recombinant R-spondin2 protein. Using Lgr5(LacZ/+) reporter mice, we demonstrate that this amplified Wnt environment leads to activation of leucine-rich repeat-containing G-protein coupled receptor 5-positive stem cells in the hair follicle. The onset of catagen is repressed by R-spondin2 injection, and the anagen phase persists. As a consequence, hair shafts grow longer. We conclude that R-spondin2 treatment activates hair follicle stem cells and therefore may have therapeutic potential to promote hair growth.
Wnt信号通路对于毛囊发育以及引发毛发周期的生长（生长期）阶段是必需的。大多数增强Wnt信号通路以促进头发生长的策略会导致Wnt组成型激活状态，这会导致上皮性毛基质发生肿瘤转化。利用Axin2（LacZ/+）和Axin2（Cre/+）R26R（mTmG/+）报告基因小鼠以及RNA分析，我们发现Wnt信号通路在生长期升高，在退行期开始时降低，并且通过皮内注射重组R-spondin2蛋白可在皮肤和周围毛囊中重新放大。利用Lgr5（LacZ/+）报告基因小鼠，我们证明这种放大的Wnt环境会导致毛囊中富含亮氨酸重复序列的G蛋白偶联受体5阳性干细胞的激活。R-spondin2注射可抑制退行期的开始，生长期持续存在。因此，毛干长得更长。我们得出结论，R-spondin2治疗可激活毛囊干细胞，因此可能具有促进头发生长的治疗潜力。
