Fundación Pablo Cassará, Instituto de Ciencia y Tecnología Dr César Milstein, Consejo Nacional de Investigaciones Científicas y Técnicas, Ciudad de Buenos Aires, Argentina.
Br J Dermatol. 2012 May;166(5):1035-42. doi: 10.1111/j.1365-2133.2012.10856.x.
Hair follicle (HF) regeneration begins when signals from the mesenchyme-derived dermal papilla cells (DPC) reach multipotent epidermal stem cells in the bulge region. Wnt/β-catenin signalling is known to affect mammalian hair growth positively. In androgenetic alopecia (AGA), androgens cause HF miniaturization through a mechanism that remains unclear. Circulating androgens act on DPC and alter paracrine factors that influence hair epithelial cells.
To elucidate the role of androgens in dermal papilla-induced differentiation of HF stem cells.
HF stem cell differentiation was evaluated in a coculture model with DPC or culturing with media conditioned by DPC after activation of androgen and Wnt/β-catenin signalling pathways. To study the molecular cross-talk between the androgen and Wnt signalling pathway in DPC, we analysed the expression and activation of downstream Wnt signalling molecules in the presence of androgens.
In a coculture model with human DPC from patients with AGA and HF stem cells, we observed that androgens abrogate hair differentiation evaluated by hair-specific keratin 6 expression. Wnt signalling activation restored the ability of androgen-treated DPC to induce differentiation. Androgen treatment revealed a significant decrease in the cytoplasmic/total β-catenin protein ratio and upregulation of the activity of glycogen synthase kinase-3β in DPC, indicative of canonical Wnt pathway inhibition.
These results suggest that androgens deregulate DPC-secreted factors involved in normal HF stem cell differentiation via the inhibition of the canonical Wnt signalling pathway.
毛囊（HF）再生始于真皮乳头细胞（DPC）从中胚层衍生而来的信号到达隆起区域的多能表皮干细胞时。已知 Wnt/β-连环蛋白信号通路正向影响哺乳动物的毛发生长。在雄激素性脱发（AGA）中，雄激素通过一种尚不清楚的机制导致 HF 缩小。循环雄激素作用于 DPC 并改变旁分泌因子，从而影响毛上皮细胞。
阐明雄激素在真皮乳头诱导 HF 干细胞分化中的作用。
在 DPC 的共培养模型中或在 DPC 激活雄激素和 Wnt/β-连环蛋白信号通路后用条件培养基培养 HF 干细胞，评估 HF 干细胞的分化。为了研究 DPC 中雄激素和 Wnt 信号通路之间的分子串扰，我们分析了存在雄激素时下游 Wnt 信号分子的表达和激活。
在来自 AGA 患者的 DPC 和 HF 干细胞的共培养模型中，我们观察到雄激素通过 hair-specific keratin 6 表达来阻止毛发生长的分化。Wnt 信号通路的激活恢复了雄激素处理的 DPC 诱导分化的能力。雄激素处理导致 DPC 中的细胞质/总β-连环蛋白蛋白比率显著降低，糖原合酶激酶-3β的活性上调，表明经典 Wnt 信号通路受到抑制。
这些结果表明，雄激素通过抑制经典 Wnt 信号通路，调节 DPC 分泌的参与正常 HF 干细胞分化的因子。
