Supplementary Material for: The Role of Fibrosis in Androgenetic Alopecia: Mechanisms and Implications

Background: Androgenetic alopecia (AGA) is a common pattern hair loss in which perifollicular fibrosis drives hair-follicle miniaturization. Inflammatory–fibrotic crosstalk centered on TGF-β/Smad, with input from Wnt/β-catenin and Notch, disrupts epithelial–mesenchymal communication and impairs regeneration. Summary: We summarize evidence linking chronic inflammation to fibroblast/myofibroblast activation and excessive extracellular-matrix deposition around hair follicles, highlight dermoscopic features that may reflect fibrotic burden, and outline a continuum between AGA and fibrosing patterned alopecias. We review anti-fibrotic strategies directed at TGF-β, Wnt/β-catenin and Notch signaling, and how combining anti-androgenic, anti-inflammatory and anti-fibrotic approaches could address both hormonal and structural drivers. Key Messages: • Perifollicular fibrosis is integral to AGA progression and may underlie incomplete treatment responses. • Dermoscopic signs such as perifollicular hyperpigmentation and whitish perifollicular structures may correlate with histologic fibrosis and merit validation. • Pathway-directed anti-fibrotic agents targeting TGF-β and Wnt/Notch show anti-fibrotic activity in other organs but require AGA-specific testing.

背景：雄激素性脱发（Androgenetic alopecia, AGA）是临床常见的斑片状脱发类型，其核心病理机制为毛囊周围纤维化（perifollicular fibrosis）介导毛囊微小化（hair-follicle miniaturization）。以转化生长因子-β/Smad（TGF-β/Smad）信号通路为核心，辅以Wnt/β-连环蛋白（Wnt/β-catenin）与Notch信号通路参与的炎症-纤维化串扰，会破坏上皮-间质通讯，损害毛囊再生能力。

总结：本综述总结了慢性炎症与毛囊周围成纤维细胞（fibroblast）/肌成纤维细胞（myofibroblast）活化及过量细胞外基质（extracellular matrix）沉积之间的关联证据；梳理了可反映纤维化负荷的皮肤镜（dermoscopic）特征；并明确了雄激素性脱发与纤维化性斑片状脱发之间的连续病理谱系。本综述同时综述了靶向TGF-β、Wnt/β-连环蛋白及Notch信号通路的抗纤维化策略，并探讨了联合抗雄激素、抗炎与抗纤维化手段，如何同时干预激素与结构层面的致病驱动因素。

核心观点：
• 毛囊周围纤维化是雄激素性脱发进展的关键环节，或可解释治疗应答不完全的潜在机制。
• 皮肤镜下的毛囊周围色素沉着、毛囊周围白色结构等体征，或与组织学纤维化程度相关，其临床价值有待进一步验证。
• 靶向TGF-β及Wnt/Notch信号通路的通路特异性抗纤维化制剂，在其他器官中已展现出抗纤维化活性，但尚需开展针对雄激素性脱发的专项研究以验证其疗效。