The central role of fibroblasts in androgenic alopecia: A systematic umbrella review.

BackgroundAndrogenic alopecia (AGA) is a common hair follicle miniaturization disease driven by androgens. Fibroblasts, especially dermal papilla (DP) cells, are considered the core of the pathogenesis of AGA, but there is a lack of systematic synthesis of evidence.ObjectiveTo systematically review the role of fibroblasts (DP cells and dermal sheath cells) in the pathogenesis of AGA, with a focus on androgen signaling transduction, paracrine signaling, disruption of stem cell niche, inflammation, and fibrosis.Data sourcesPubMed and Web of Science, covering the period from August 23, 2025 to May 28, 2026, including human basic research, animal model studies, and clinical pathology studies related to AGA fibroblast function. Two reviewers independently screened literature, extracted data, and evaluated the risk of bias.ResultThrough retrieval, a total of 1592 articles were identified, and 43 articles were ultimately included. DP cells consistently express high levels of androgen receptor (AR) and 5α-reductase type II. Activation of androgens (dihydrotestosterone) in DP cells leads to: (1) downregulation of Wnt/β-catenin signaling and upregulation of TGF-β/BMP pathway; (2) Changes in secretion profile (decrease in VEGF/IGF-1 and increase in DKK-1/TGF-β1); (3) DP cell aggregation behavior is impaired; (4) Destruction of hair follicle stem cell activation; (5) Inducing inflammation and fibrosis around hair follicles. The evidence for dermal sheath cells as a DP cell bank is still limited.ConclusionDP cells are the main transducers of androgen signaling in AGA, driving follicle miniaturization through multiple interrelated mechanisms. The current evidence supports DP cell dysfunction as a therapeutic strategy.