IL-36α Promoted Wound Induced Hair Follicle Neogenesis via Hair Follicle Stem/Progenitor Cell Proliferation

Background: Wound-induced hair follicle neogenesis (WIHN) is a phenomenon of hair neogenesis that occurs at the center of a scar when the wound area is sufficiently large. Neogenic hair follicles are separated from the pre-existing follicles at the wound edge by a hairless circular region. This WIHN study provides a unique model for developing treatments for hair loss and deciphering the mechanisms underlying organogenesis in adult mammals. Methods: The skin of a mouse was wounded by excising a 1.5 x 1.5 cm(2) square of full-thickness dorsal skin. iTRAQ technology was used to screen proteins differentially expressed between the inner and outer scar areas in a mouse model of WIHN, on post-wounding day 15, to identify the regulators of WIHN. Owing to the overexpression of interleukin-36 alpha (IL-36 alpha) in thede novohair follicle growth area, the regulating effect of IL-36 alpha overexpression in WIHN was investigated. Hair follicle stem/progenitor cells were counted by flow cytometry while the expression of hair follicle stem/progenitor cell markers (Lgr5, Lgr6, Lrig1, K15, andCD34) and that of Wnt/beta-catenin and IL-6/STAT3 pathway intermediaries was detected by qPCR and western blotting. Results: We found that wounding induced IL-36 alpha expression. Incorporation of recombinant murine IL-36 alpha (mrIL-36 alpha) into murine skin wounds resulted in a greater number of regenerated hair follicles (p< 0.005) and a faster healing rate. The expression of hair follicle stem/progenitor cell markers was upregulated in the mrIL-36 alpha-injected site (p< 0.05). Additionally, mrIL-36 alpha upregulated the IL-6/STAT3 pathway : intermediaries. Conclusion: IL-36 alpha is upregulated inde novohair follicle growth areas and can promote wound epithelialization and WIHN.