Small cutaneous wounds induce telogen to anagen transition of murine hair follicle stem cells

Background: Recent studies suggest that large (>1 cm) diameter circular cutaneous wounds induce follicular neogenesis in mice. However, the effects of non-circular wounds or smaller circular wounds on the hair follicle cycle remain poorly understood. Objective: We investigated whether non-circular wounds or smaller (<= 1 cm) circular wounds could induce early entry of hair follicle stem cells into anagen. Methods: We created different shaped and sized full-thickness incisional wounds on the dorsal skin of 6-wk old mice (BALB/c, C57BL/6, and CD1), and then assessed for hair growth, wound contraction rates, and growth factor and/or immunomodulatory cytokine involvement. Results: By day 16 and through day 26 post-wounding, we observed hair growth in the skin around the wound, but not in distant unwounded skin of BALB/c and C57BL/6 mice. In contrast, CD1 mice showed hair growth in both the wounded and unwounded skin. In all mice, the hair growth pattern was independent of wound type. The area of hair growth induced by a 2 cm linear wound was roughly 2-fold that induced by a 1 cm linear wound and 4-fold that of a 0.5 cm linear wound. Increased gamma-glutamyl transpeptidase activity was observed in hair follicles growing in the wounded area as well as an up to 8-fold upregulation of Wnt- and Shh-dependent signaling, consistent with anagen growth. Conclusion: Our data strongly support that small cutaneous wounds induce telogen to anagen transition of murine hair follicle stem cells. (C) 2010 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.