Department of Immunology, School of Medicine, Kyungpook National University, Daegu, Korea.
J Invest Dermatol. 2012 Jun;132(6):1554-60. doi: 10.1038/jid.2012.24. Epub 2012 Feb 23.
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 β-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.
最近，我们提出 Dickkopf 1（DKK-1）是一种参与男性型脱发的致病介质。由于早期退行期的发生是男性型脱发的一个关键特征，在这项研究中，我们评估了 DKK-1 是否作为毛发周期中的退行期诱导剂发挥作用。在此，我们报告重组人 DKK-1（rhDKK-1）在毛发生长期内注射到小鼠的真皮下会导致退行期的过早发生，而中和 DKK-1 的抗体则会延迟小鼠的毛发生长期到退行期的转变。此外，rhDKK-1 的治疗导致终末毛囊长度减少，而 DKK-1 抗体则导致与对照动物相比增加。此外，DKK-1 和 DKK-1 信使 RNA 的表达在脱毛诱导的毛发周期进展中晚期毛发生长期的毛囊角质形成细胞中上调最明显。此外，我们观察到 rhDKK-1 阻断了经典 Wnt 介导的β-连环蛋白信号的激活，并诱导了促凋亡蛋白 Bax，导致外根鞘角质形成细胞凋亡。总之，我们的数据强烈表明 DKK-1 通过调节毛囊角质形成细胞的活性参与毛发生长期到退行期的转变。
