Dickkopf 1 Promotes Regression of Hair Follicles
Dickkopf 1 Promotes Regression of Hair Follicles
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DOI：
10.1038/jid.2012.24
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发表时间：
2012-06-01
影响因子：
6.5
通讯作者：
Sung, Young K.
中科院分区：
文献类型：
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作者：
Kwack, Mi H.;Kim, Moon K.;Sung, Young K.
最近，我们提出Dickkopf 1（DKK-1）是一个致病介质参与男性型秃发。由于过早的退行期发作是男性型秃发的一个关键特征，在这项研究中，我们评估了DKK-1是否在毛发周期中作为退行期诱导剂的作用。在此，我们报告，重组人DKK-1（rhDKK-1）注射到皮下组织的小鼠在生长期引起过早的退行期，而中和DKK-1抗体延迟生长期到退行期的小鼠过渡。此外，与对照动物相比，用rhDKK-1治疗导致最终毛囊长度减少，而DKK-1抗体导致最终毛囊长度增加。此外，在脱毛诱导的毛发周期进展中，DKK-1和DKK-1信使RNA表达在生长期晚期的毛囊角质形成细胞中上调最多。此外，我们观察到rhDKK-1阻断经典Wnt介导的β-连环蛋白信号转导的激活，并诱导促凋亡蛋白Bax，导致外根鞘角质形成细胞的凋亡。综上所述，我们的数据有力地表明，DKK-1参与毛发周期中的生长期到退化期的过渡，通过调节毛囊角质形成细胞的活性。
Recently, we suggested that Dickkopf 1 (DKK-1) is a pathogenic mediator involved in male pattern baldness. As premature catagen onset is a key characteristic of male pattern baldness, in this study, we evaluated whether DKK-1 has a role as a catagen inducer in hair cycling. Herein, we report that recombinant human DKK-1 (rhDKK-1) injection into the hypodermis of mice during anagen caused premature onset of catagen, whereas neutralizing DKK-1 antibody delayed anagen-to-catagen transition in mice. Moreover, treatment with rhDKK-1 led to a decrease in final hair follicle length, whereas DKK-1 antibody led to an increase compared with control animals. In addition, DKK-1 and DKK-1 messenger RNA expression is most upregulated in follicular keratinocytes of late anagen in depilation-induced hair cycle progression. Moreover, we observed that rhDKK-1 blocks canonical Wnt-mediated activation of beta-catenin signaling and induces the proapoptotic protein Bax, resulting in apoptosis in outer root sheath keratinocytes. Taken together, our data strongly suggest that DKK-1 is involved in anagen-to-catagen transition in the hair cycle by regulating the activity of follicular keratinocytes.