No abstract

Epiregulin (EPR) is a broad specificity EGF family member that activates ErbB1 and ErbB4 homodimers and all possible heterodimeric ErbB complexes. We have previously shown that topical EPR enhances the repair of murine excisional wounds. The purpose of this study was to determine whether EPR was more effective than EGF or TGFalpha in promoting in vitro wound closure and to compare the EPR induced signal transduction pathways with those activated by EGF and TGFalpha. Normal human epidermal keratinocytes or A431 cells were scratch wounded and treated for 24 h with varying doses of EPR, EGF or TGFalpha. Five-fold lower doses of EPR were significantly better than EGF or TGFalpha in stimulating in vitro wound closure. Mitomycin-c reduced EPR induced wound closure by 59%, versus a 9% and 25% decrease in EGF and TGFalpha induced closure. The ERK/MAPK inhibitor PD-98059 decreased EPR induced wound closure by 88%. By contrast, the PLC inhibitor U-73122, only reduced the EPR induced response by 21%. Immunoblot analysis revealed that 2 nM EPR stimulated a six-fold increase in p-ERK1/2, whereas 10 nM EGF or TGFalpha stimulated only a 3- and 2.5-fold increase in p-ERK1/2. When compared with EGF or TGFalpha, EPR is a more potent and more effective inducer of in vitro wound closure due to its ability to promote significantly greater ERK/MAPK activation.

No abstract

Diffuse dermal angiomatosis (DDA) is an acquired, benign vascular proliferation characterized clinically by poorly circumscribed, violaceous, livedoid plaques with frequent ulceration. Histologically, a diffuse interstitial proliferation of CD31-positive endothelial cells is present within the papillary and reticular dermis. Endothelial atypia, atypical mitoses, and vasculitis are lacking. We describe a case of DDA in a 53-year-old man with peripheral vascular atherosclerosis that resolved following revascularization. Early correction of the associated ischemic peripheral vascular disease promotes resolution of this unusual clinicopathologic entity.

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 micro g/ml), epidermal growth factor (10 micro g/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.