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Updated: Mar 12, 2026

Rapid Genetic Analysis of Epithelial-Mesenchymal Signaling During Hair Regeneration
Published on: February 28, 2013
Alkaline Phosphatase-Regulated C-C Motif Chemokine Ligand 5 (CCL5) Functions as a Critical Mediator of Hair Follicle
Mi Hee Kwack1, Myungsu Jung2, Young Kwan Sung3
1Department of Immunology, School of Medicine, Kyungpook National University, 680 Gukchaebosang-ro, Jung-gu, Daegu, 41944, Korea. go3004@knu.ac.kr.
Background:
Alkaline 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.
Methods:
A 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.
Results:
ALP 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.
Conclusion:
These 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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