Topical epiregulin enhances repair of murine excisional wounds

Epiregulin is a broad specificity epidermal growth factor family member that activates ErbB1 and ErbB4 homodimers and all possible heterodimeric ErbB complexes. Our objective was to determine whether topical epiregulin enhanced repair of murine excisional wounds. Wounds were treated on days 0-4 with either topical epiregulin (1 mug/ml), epidermal growth factor (10 mug/ml), or vehicle. At day 5 postinjury, wounds receiving epiregulin were significantly smaller than those treated with epidermal growth factor or vehicle. Treatment with epiregulin promoted greater epidermal proliferation and thickening than epidermal growth factor or vehicle due to an expansion of the proliferative compartment of keratinocytes. Dermal thickness was also increased in epiregulin-treated wounds as compared to those treated with epidermal growth factor or vehicle. In day 5 wounds, matrix metalloproteinase-3 (stromelysin-1) mRNA levels were significantly lower in epiregulin- or epidermal growth factor-treated wounds than in vehicle-treated controls, suggesting that growth factor-treated wounds were more mature and required less ongoing proteolytic activity than their same-day vehicle-treated counterparts. This is the first report that topical epiregulin accelerates repair of full-thickness murine excisional wounds as compared to vehicle or epidermal growth factor. Furthermore, epiregulin is more potent and more effective than epidermal growth factor in promoting proliferation and maturation of the epidermis as well as enhancement of the neodermis.