Adenovirus-Mediated Wnt10b Overexpression Induces Hair Follicle Regeneration

Adenovirus-Mediated Wnt10b Overexpression Induces Hair Follicle Regeneration
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腺病毒介导的 Wnt10b 过表达诱导毛囊再生

DOI:
10.1038/jid.2012.235
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发表时间:
2013-01-01
影响因子:
6.5
通讯作者:
Yang, Tian
Yang, Tian
中科院分区:
医学1区
文献类型:
--
作者:
Li, Yu-Hong;Zhang, Kun;Yang, Tian

文献摘要

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毛囊周期性地进行再生。激活剂和抑制剂之间的平衡可能决定休止期毛囊重新进入生长期所需的时间。我们以前报道过Wnt 10 b(wingless-type mouse mammary tumor virus integration site family member 10 b)在体外可以促进毛囊的生长。为了揭示Wnt 10 b在毛囊再生中的作用,我们建立了一个皮内注射的体内小鼠模型。在此模型的基础上,我们发现Wnt 10 b在皮肤中过表达时可以诱导毛囊从休止期到生长期的生物转换。诱导后的毛囊表达结构标志物,并能正常进入退行期。相反,通过用小干扰RNA(siRNA)敲低Wnt 10 b,取消生长期开始。Wnt 10 b的异常表达数据表明,它是毛囊再生的激活剂之一。在Wnt 10 b诱导的毛囊中,P-连环蛋白易位到细胞核。当用siRNA下调P-catenin表达时,Wnt 10 b的生物学效应被废除。这些数据表明,Wnt 10 b可能通过增强经典Wnt信号通路的激活来诱导体内毛囊再生。据我们所知,我们的数据提供了以前未报道的毛囊周期调控的见解,并为毛囊相关疾病提供了潜在的治疗靶点。Journal of Investigative Dermatology(2013)133,42-48; doi:10.1038/jid.2012.235; 2012年7月26日在线发表
Hair follicles periodically undergo regeneration. The balance between activators and inhibitors may determine the time required for telogen hair follicles to reenter anagen. We previously reported that Wnt10b (wingless-type mouse mammary tumor virus integration site family member 10b) could promote the growth of hair follicles in vitro. To unveil the roles of Wnt10b in hair follicle regeneration, we established an in vivo mouse model using intradermal injection. On the basis of this model, we found that Wnt10b could induce the biological switch of hair follicles from telogen to anagen when overexpressed in the skin. The induced hair follicles expressed structure markers and could cycle normally into catagen. Conversely, anagen onset was abrogated by the knockdown of Wnt10b with small interfering RNA (siRNA). The Wnt10b aberrant expression data suggest that it is one of the activators of hair follicle regeneration. The P-catenin protein is translocated to the nucleus in Wnt10b-induced hair follicles. The biological effects of Wnt10b were abrogated when P-catenin expression was downregulated with siRNA. These data revealed that Wnt10b might induce hair follicle regeneration in vivo via the enhanced activation of the canonical Wnt signaling pathway. To our knowledge, our data provide previously unreported insights into the regulation of hair follicle cycling and provide potential therapeutic targets for hair follicle-related diseases. Journal of Investigative Dermatology (2013) 133, 42-48; doi:10.1038/jid.2012.235; published online 26 July 2012