Increased rate of hair regrowth in mice with constitutive over expression of the angiogenic factor Del1 in basal keratinocytes

Abstract

Abstract Introduction: Del1 is a secreted extracellular matrix-associated protein that stimulates angiogenesis through integrin binding and is implicated in vasculogenesis. We used transgenic mice engineered to over-express Del1 in the skin to examine the effect of increased Del1 in wound healing. No effect was found on wound healing, but we found an increased rate of hair regrowth. Methods: Del1 was cloned behind a keratin 14 promoter (K14-Del1) that drives constitutive expression in the basal keratinocytes and this construct was used to generate two separate transgenic mouse lines. 6–8 week old transgenic animals were shaved and depilated with Nair along the posterior midline. Wild-type littermates were used as controls, and tissues were harvested at 10, 12, 14, 15, and 18 days post-depilation. Progress of hair regrowth was followed by photography, histology, and immunohistochemistry. Results: K14-Del1 animals appear normal and heal excisional wounds normally. Immunohistochemistry confirmed increased Del1 expression, but indicated no increase in vascularity. Following depilation, hair regrowth was grossly visible by day 15 in littermates compared to day 18 for normals. Full-length hair follicles were visible by histology at post-depilation day 15 in K14-Del1 animals, while wild type animals showed very rudimentary hair-follicle regeneration. Conclusions: Constitutive expression of Del1 in skin does not appear to increase vascularity or improve wound healing. Surprisingly, we found this led to increased hair regrowth following depilation. Depilation is a known inducer of hair anagenesis and Del1 appears to speed this process. Future studies will elucidate a mechanism for this phenotype.