Roles of GasderminA3 in Catagen-Telogen Transition During Hair Cycling.
Roles of GasderminA3 in Catagen-Telogen Transition During Hair Cycling.
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DOI：
10.1038/jid.2015.147
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发表时间：
2015-09
期刊：
影响因子：
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通讯作者：
Lian X
中科院分区：
文献类型：
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作者：
Bai X;Lei M;Shi J;Yu Y;Qiu W;Lai X;Liu Y;Yang T;Yang L;Widelitz RB;Chuong CM;Lian X
在出生后的生活中，毛囊经历了退化（退化）、休止（休止）和再生（生长）的循环行为。头发周期的转变受到自主和外在分子环境的严格调控。然而，是否有一种开关控制着催动-休止转换，在很大程度上仍然是未知的。在这里，我们展示了毛囊在Gsdma3突变后从发育期到下一个生长期的循环，而不是通过形态学上典型的休眠期过渡。这在WT小鼠的休止期留下了ESLS（上皮链状结构）。从分子上看，Wnt10b在Gsdma3突变小鼠中上调。恢复Gsdma3在AE（秃剥）小鼠皮肤中的表达可挽救毛囊进入停止期，并显著降低wnt10b介导的Wnt/β-catenin信号通路。过表达Wnt10b通过增加上皮链细胞增殖抑制休止期进入。随后，Gsdma3突变的毛囊与WT小鼠一样同时进入第二生长期。异位WT Gsdma3过表达的毛囊不能进入第二生长期。荧光素酶报告基因实验证实Gsdma3直接抑制Wnt信号。我们的研究结果表明，Gsdma3通过平衡Wnt信号通路在休止期转变过程中发挥重要作用，并且形态上典型的休止期对于新头发周期的开始不是必需的。
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 Gsdma3 directly suppresses Wnt signaling. Our findings suggest Gsdma3 plays 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.