Inserm UMR976, Skin Research Institute, F-75475, Paris, France.
University Paris Diderot, Sorbonne Paris-Cité, Hôpital Saint-Louis, F-75475, Paris, France.
Br J Dermatol. 2017 Nov;177(5):1322-1336. doi: 10.1111/bjd.15577. Epub 2017 Oct 25.
Male androgenetic alopecia (AGA) is the most common form of hair loss in men. It is characterized by a distinct pattern of progressive hair loss starting from the frontal area and the vertex of the scalp. Although several genetic risk loci have been identified, relevant genes for AGA remain to be defined.
To identify biomarkers associated with AGA.
Molecular biomarkers associated with premature AGA were identified through gene expression analysis using cDNA generated from scalp vertex biopsies of hairless or bald men with premature AGA, and healthy volunteers.
This monocentric study reveals that genes encoding mast cell granule enzymes, inflammatory mediators and immunoglobulin-associated immune mediators were significantly overexpressed in AGA. In contrast, underexpressed genes appear to be associated with the Wnt/β-catenin and bone morphogenic protein/transforming growth factor-β signalling pathways. Although involvement of these pathways in hair follicle regeneration is well described, functional interpretation of the transcriptomic data highlights different events that account for their inhibition. In particular, one of these events depends on the dysregulated expression of proopiomelanocortin, as confirmed by polymerase chain reaction and immunohistochemistry. In addition, lower expression of CYP27B1 in patients with AGA supports the notion that changes in vitamin D metabolism contributes to hair loss.
This study provides compelling evidence for distinct molecular events contributing to alopecia that may pave the way for new therapeutic approaches.
男性雄激素性脱发（AGA）是男性最常见的脱发形式。其特征是从额部和头皮顶点开始出现明显的进行性脱发模式。尽管已经确定了几个遗传风险位点，但 AGA 的相关基因仍有待确定。
确定与 AGA 相关的生物标志物。
通过对无发或秃顶的 AGA 男性和健康志愿者的头皮顶点活检生成的 cDNA 进行基因表达分析，鉴定与过早 AGA 相关的分子生物标志物。
这项单中心研究表明，编码肥大细胞颗粒酶、炎症介质和免疫球蛋白相关免疫介质的基因在 AGA 中表达显著上调。相比之下，下调表达的基因似乎与 Wnt/β-catenin 和骨形态发生蛋白/转化生长因子-β信号通路有关。尽管这些通路在毛囊再生中的作用已得到充分描述，但对转录组数据的功能解释突出了导致其抑制的不同事件。特别是，其中一个事件依赖于前阿黑皮素原的失调表达，这一点通过聚合酶链反应和免疫组织化学得到了证实。此外，AGA 患者 CYP27B1 表达降低支持了维生素 D 代谢变化导致脱发的观点。
这项研究为导致脱发的不同分子事件提供了令人信服的证据，可能为新的治疗方法铺平道路。
