ArticleTissue engineering and regenerative medicine2026
Alkaline Phosphatase-Regulated C-C Motif Chemokine Ligand 5 (CCL5) Functions as a Critical Mediator of Hair Follicle Neogenesis.
Article in Tissue engineering and regenerative medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundAlkaline phosphatase (ALP) is a well-established molecular marker of dermal papilla (DP) cells, and its activity closely correlates with their hair-inductive (trichogenic) capacity. This study aimed to identify downstream effectors regulated by ALP that contribute to trichogenicity, and to validate their functional significance in hair follicle neogenesis.
methodsA cytokine array was employed to screen ALP-dependent secreted factors in three-dimensional (3D) cultured human DP spheres. The expression of C-C motif chemokine ligand 5 (CCL5) and its receptor C-C chemokine receptor type 1 (CCR1) was confirmed by quantitative real-time PCR and immunohistochemistry in human hair follicles and murine skin. Functional roles of CCL5 in DP spheres and CCR1 in mouse epidermal cells were evaluated using siRNA-mediated knockdown followed by in vivo patch hair regeneration assays.
resultsALP knockdown significantly reduced CCL5 expression in DP spheres. Silencing of CCL5 in DP spheres markedly decreased their hair-inductive capacity, while CCR1 knockdown in epidermal cells impaired hair follicle formation. Combined knockdown of CCL5 in DP cells and CCR1 in epidermal cells completely abolished hair follicle neogenesis.
conclusionThese findings identify CCL5 as a critical downstream mediator of ALP-regulated trichogenicity in human DP spheres, with CCR1 serving as its essential receptor in epidermal cells. The ALP-CCL5-CCR1 axis represents a promising therapeutic target for promoting hair regeneration.
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