Epiregulin is more potent than EGF or TGFalpha in promoting in vitro wound closure due to enhanced XXXX /MAPK activation.

@entity1 @entity470 @entity12251 @entity19 @entity3963
Epiregulin (EPR) is a broad specificity EGF family member that activates @entity470 and @entity12251 homodimers and all possible heterodimeric @entity470 complexes. We have previously shown that topical EPR enhances the repair of @entity19 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 @entity1 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 @entity3963 /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 @entity3963 /MAPK activation.
