Lee Seon Bok, Lee Jae Won, Lee Hyemin, Lee Kyung-Ju, Hwang Hye Won, Shin Hyun-Tae, Byun Ji Won, Shin Jeonghyun, Choi Gwang Seong
Department of Dermatology, Inha University School of Medicine, Incheon, Korea.
Ann Dermatol. 2024 Oct;36(5):292-299. doi: 10.5021/ad.23.128.
The Wnt/β-catenin signaling pathway is crucial for the development, initiation, and growth of hair follicles (HFs). The Dickkopf-related protein (DKK) gene family encodes secreted proteins modulating the Wnt/β-catenin signaling pathway. Studies have reported that DKK1 promotes the regression of HFs and serves as a pathogenic mediator in male pattern baldness. However, the role of DKK2 on human hair growth has not yet been explored.
This study investigates direct effect of DKK2 on hair growth using human dermal papilla cell (DPC) cultures and human HF organ cultures.
To elucidate the effect of DKK2 on hair growth, we examined the effect of recombinant human DKK2 (rhDKK2) treatment on cell viability, expression of mRNA and protein related to the Wnt/β-catenin signaling pathway, and cell growth in cultured human DPCs. We also performed organ culture of HFs with rhDKK2 and measured changes in hair shaft length for 8 days.
Treatment with rhDKK2 led to a dose-dependent rise in the proliferation of human DPCs (<0.05), reaching levels comparable to those induced by 1 μM minoxidil. Moreover, rhDKK2 increased the expression of Wnt/β-catenin target genes, phosphorylated extracellular signal-regulated kinase, and cyclin-D1; it also increased the BAX-to-Bcl-2 ratio and downregulated the bone morphogenetic protein 2 gene. In human HF organ cultures, relative to the control treatment, rhDKK2 treatment significantly increased hair shaft elongation (<0.01).
Our results indicate that rhDKK2 could promote hair growth by facilitating the proliferation of human DPCs through activation of the Wnt/β-catenin signaling pathway.
Wnt/β-连环蛋白信号通路对毛囊的发育、起始和生长至关重要。Dickkopf相关蛋白（DKK）基因家族编码调节Wnt/β-连环蛋白信号通路的分泌蛋白。研究报道，DKK1促进毛囊退化，并在男性型秃发中作为致病介质。然而，DKK2对人类头发生长的作用尚未得到探索。
本研究使用人真皮乳头细胞（DPC）培养物和人毛囊器官培养物研究DKK2对头发生长的直接影响。
为阐明DKK2对头发生长的影响，我们检测了重组人DKK2（rhDKK2）处理对培养的人DPCs的细胞活力、与Wnt/β-连环蛋白信号通路相关的mRNA和蛋白表达以及细胞生长的影响。我们还用rhDKK2进行了毛囊器官培养，并测量了8天内毛干长度的变化。
rhDKK2处理导致人DPCs增殖呈剂量依赖性增加（P<0.05），达到与1μM米诺地尔诱导的水平相当。此外，rhDKK2增加了Wnt/β-连环蛋白靶基因、磷酸化细胞外信号调节激酶和细胞周期蛋白D1的表达；它还增加了BAX与Bcl-2的比值，并下调了骨形态发生蛋白2基因。在人毛囊器官培养中，相对于对照处理，rhDKK2处理显著增加了毛干伸长（P<0.01）。
我们的结果表明，rhDKK2可通过激活Wnt/β-连环蛋白信号通路促进人DPCs增殖，从而促进头发生长。
