Bai Xiufeng, Lei Mingxing, Shi Jiazhong, Yu Yu, Qiu Weiming, Lai Xiangdong, Liu Yingxin, Yang Tian, Yang Li, Widelitz Randall B, Chuong Cheng-Ming, Lian Xiaohua
Department of Cell Biology, Third Military Medical University, Chongqing, People's Republic of China.
Key Laboratory of Biorheological Science and Technology, Ministry of Education, Bioengineering College, Chongqing University, Chongqing, People's Republic of China; '111' Project Laboratory of Biomechanics and Tissue Repair, Bioengineering College, Chongqing University, Chongqing, People's Republic of China; Department of Pathology, University of Southern California, Los Angeles, California, USA.
J Invest Dermatol. 2015 Sep;135(9):2162-2172. doi: 10.1038/jid.2015.147. Epub 2015 Apr 10.
Hair follicles undergo cyclic behavior through regression (catagen), rest (telogen), and regeneration (anagen) during postnatal life. The hair cycle transition is strictly regulated by the autonomous and extrinsic molecular environment. However, whether there is a switch controlling catagen-telogen transition remains largely unknown. Here we show that hair follicles cycle from catagen to the next anagen without transitioning through a morphologically typical telogen after Gsdma3 mutation. This leaves an ESLS (epithelial strand-like structure) during the time period corresponding to telogen phase in WT mice. Molecularly, Wnt10b is upregulated in Gsdma3 mutant mice. Restoration of Gsdma3 expression in AE (alopecia and excoriation) mouse skin rescues hair follicle telogen entry and significantly decreases the Wnt10b-mediated Wnt/β-catenin signaling pathway. Overexpression of Wnt10b inhibits telogen entry by increasing epithelial strand cell proliferation. Subsequently, hair follicles with a Gsdma3 mutation enter the second anagen simultaneously as WT mice. Hair follicles cannot enter the second anagen with ectopic WT Gsdma3 overexpression. A luciferase reporter assay proves that Gsdma3 directly suppresses Wnt signaling. Our findings suggest that Gsdma3 has an important role in catagen-telogen transition by balancing the Wnt signaling pathway and that morphologically typical telogen is not essential for the initiation of a new hair cycle.
毛囊在出生后的生命过程中经历周期性变化，包括退行期（生长期）、静止期（休止期）和再生期（生长期）。毛发周期的转换受到自主和外在分子环境的严格调控。然而，是否存在控制生长期向休止期转换的开关仍 largely unknown。在这里，我们表明，在Gsdma3突变后，毛囊从生长期循环到下一个生长期，而无需通过形态学上典型的休止期进行转换。这在与野生型小鼠休止期相对应的时间段内留下了一种上皮条索样结构（ESLS）。在分子水平上，Wnt10b在Gsdma3突变小鼠中上调。在AE（脱发和擦伤）小鼠皮肤中恢复Gsdma3表达可挽救毛囊进入休止期，并显著降低Wnt10b介导的Wnt/β-连环蛋白信号通路。Wnt10b的过表达通过增加上皮条索细胞增殖来抑制休止期的进入。随后，具有Gsdma3突变的毛囊与野生型小鼠同时进入第二个生长期。毛囊不能通过异位过表达野生型Gsdma3进入第二个生长期。荧光素酶报告基因检测证明Gsdma3直接抑制Wnt信号。我们的研究结果表明，Gsdma3在生长期向休止期的转换中通过平衡Wnt信号通路发挥重要作用，并且形态学上典型的休止期对于新毛发周期的启动并非必不可少。
