Wnt信号通路
细胞生物学
干细胞
毛乳头
旁分泌信号
雄激素
毛囊
连环素
生物
内分泌学
细胞分化
内科学
化学
信号转导
医学
受体
生物化学
激素
基因
作者
Gustavo José Leirós,Alejandra Attorresi,María Eugenia Balañá
标识
DOI:10.1111/j.1365-2133.2012.10856.x
摘要
Summary Background 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. Objectives To elucidate the role of androgens in dermal papilla-induced differentiation of HF stem cells. Methods 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. Results 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. Conclusions 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.
科研通智能强力驱动
Strongly Powered by AbleSci AI