Keratinocyte Growth Inhibition through the Modification of Wnt Signaling by Androgen in Balding Dermal Papilla Cells
Keratinocyte Growth Inhibition through the Modification of Wnt Signaling by Androgen in Balding Dermal Papilla Cells
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DOI：
10.1210/jc.2008-1053
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发表时间：
2009-04-01
影响因子：
5.8
通讯作者：
Kawata, Mitsuhiro
中科院分区：
文献类型：
--
作者：
Kitagawa, Tomoko;Matsuda, Ken-Ichi;Kawata, Mitsuhiro
背景/目的：雄激素诱导雄激素性脱发（AGA），它对头皮额部的头发生长有退行性影响。相反，已知Wnt蛋白对哺乳动物毛发生长有积极影响。我们假设雄激素通过与Wnt信号系统的相互作用来减少头发生长。本研究旨在探讨雄激素对真皮乳头（DP）细胞Wnt信号传导的影响。设计：使用由DP细胞和角质形成细胞组成的共培养系统，测量雄激素和Wnt3a对角质形成细胞增殖的影响。通过分析雄激素受体（AR）和下游Wnt信号分子的表达、胞内定位和活性，探讨雄激素和Wnt通路在DP细胞中相互作用的分子机制。结果：在与来自AGA患者的DP细胞共培养时，添加双氢睾酮可抑制wnt3a依赖性角化细胞的生长，但与来自非AGA男性的DP细胞共培养时，生长不受抑制。尽管来自两个头皮区域的DP细胞都表达AR蛋白，但AGA患者的DP细胞中AR和与β -连环蛋白（一种下游Wnt信号分子）共易位的表达水平高于非AGA男性的DP细胞。此外，仅在AGA患者的DP细胞中观察到Wnt信号介导的转录对双氢睾酮治疗的显著抑制。结论：DP细胞Wnt信号通路受雄激素调控，在雄激素对毛发生长的影响中起关键作用。[J] .中华内分泌杂志，2009,31(4):387 - 398。
Context/Objective: Androgen induces androgenetic alopecia (AGA), which has a regressive effect on hair growth from the frontal region of the scalp. Conversely, Wnt proteins are known to positively affect mammalian hair growth. We hypothesized that androgen reduces hair growth via an interaction with the Wnt signaling system. The objective of this study was to investigate the effect of androgen on Wnt signaling in dermal papilla (DP) cells.Design: The effect of androgen and Wnt3a on keratinocyte proliferation was measured by use of a coculture system consisting of DP cells and keratinocytes. The molecular mechanisms of androgen and Wnt pathway interactions in DP cells were examined by analyzing the expression, intracellular localization, and activity of the androgen receptor (AR) and also downstream Wnt signaling molecules.Results: Wnt3a-dependent keratinocyte growth was suppressed by the addition of dihydrotestosterone in coculture with DP cells that were derived from AGA patients, but growth was not suppressed in coculture with DP cells from non-AGA males. Whereas DP cells from both scalp regions expressed AR protein, the expression levels of AR and cotranslocation with beta-catenin, a downstream Wnt signaling molecule, were higher in DP cells of AGA patients than in DP cells from non-AGA males. In addition, significant suppression of Wnt signal-mediated transcription in response to dihydrotestosterone treatment was observed only in DP cells from AGA patients.Conclusion: These results suggest that Wnt signaling in DP cells is regulated by androgen and this regulation plays a pivotal role in androgen's action on hair growth. (J Clin Endocrinol Metab 94: 1288-1294, 2009)