Kwack Mi Hee, Sung Young Kwan, Chung Eun Jung, Im Sang Uk, Ahn Ji Seop, Kim Moon Kyu, Kim Jung Chul
Department of Immunology, School of Medicine, Kyungpook National University, Daegu, Korea.
J Invest Dermatol. 2008 Feb;128(2):262-9. doi: 10.1038/sj.jid.5700999. Epub 2007 Jul 26.
Recent studies suggest that androgen-driven alteration to the autocrine and paracrine factors produced by scalp dermal papilla (DP) cells may be a key to androgen-potentiated balding. Here, we screened dihydrotestosterone (DHT)-regulated genes in balding DP cells and found that dickkopf 1 (DKK-1) is one of the most upregulated genes. DKK-1 messenger RNA is upregulated in 3-6 hours after 50-100 nM DHT treatment and ELISA showed that DKK-1 is secreted from DP cells in response to DHT. A co-culture system using outer root sheath (ORS) keratinocytes and DP cells showed that DHT inhibits the growth of ORS cells, and neutralizing antibody against DKK-1 significantly reversed the growth inhibition of ORS cells. Analysis of co-cultured ORS cells showed a significant increment of sub-G1 apoptotic cells in response to DHT. Also, recombinant human DKK-1 inhibited the growth of ORS cells and triggered apoptotic cell death. In addition, DHT-induced epithelial cell death in cultured hair follicles was reversed by neutralizing DKK-1 antibody. Moreover, immunoblotting showed that the DKK-1 level is up in the bald scalp compared with the haired scalp of patients with androgenetic alopecia. Altogether, our data strongly suggest that DHT-inducible DKK-1 is involved in DHT-driven balding.
近期研究表明，雄激素驱动的头皮真皮乳头（DP）细胞产生的自分泌和旁分泌因子改变可能是雄激素性脱发加重的关键。在此，我们筛选了雄激素性脱发DP细胞中双氢睾酮（DHT）调控的基因，发现Dickkopf 1（DKK-1）是上调最为显著的基因之一。在50-100 nM DHT处理后3-6小时，DKK-1信使核糖核酸上调，酶联免疫吸附测定显示，DP细胞会响应DHT分泌DKK-1。使用外根鞘（ORS）角质形成细胞和DP细胞的共培养系统显示，DHT抑制ORS细胞的生长，而针对DKK-1的中和抗体可显著逆转ORS细胞的生长抑制。对共培养的ORS细胞分析显示，响应DHT时，亚G1期凋亡细胞显著增加。此外，重组人DKK-1抑制ORS细胞的生长并引发凋亡性细胞死亡。另外，中和DKK-1抗体可逆转培养毛囊中DHT诱导的上皮细胞死亡。而且，免疫印迹显示，与雄激素性脱发患者有头发的头皮相比，秃发头皮中的DKK-1水平升高。总之，我们的数据强烈表明，DHT诱导的DKK-1参与了DHT驱动的脱发过程。
