Modulation of porcine wound repair with a transfected ErbB3 gene and relevant EGF-like ligands.
Our in vivo study used an ErbB3 receptor transfection strategy to determine if topical application of EGF-like ligands would enhance repair. Partial-thickness porcine wounds transfected with adenoviral particles containing an ErbB3 receptor gene or a vehicle beta-galactosidase gene were introduced and wounds were concomitantly supplied with a variety of EGF-like ligands--EGF, epiregulin (EPR), heparin binding EGF (HB-EGF), and heregulin/neuregulin (HRG). Comparisons of cutaneous repair (resurfacing, dermal depth, proliferation, macrophage infiltration, microvascular density, apoptosis) were assessed after a 5-day healing interval. Differential effects were noted. In wounds transfected with additional ErbB3, either EPR or HB-EGF promoted resurfacing greater than EGF, HRG, or controls. Dermal responses differed significantly after EPR or HB-EGF treatments compared to EGF, HRG, ErbB3 only, or empty vehicle. Hallmarks of enhanced wound maturity were noted in EPR- and HB-EGF-treated wounds transfected with ErbB3. Our data confirmed that an ErbB3-driven pathway mediates a net positive influence in an in vivo model closely resembling human repair. The sensitivity in this system was sufficient to reveal differential outcomes following stimulation with various EGF ligands. We conclude that selective stimulation through an ErbB3-driven pathway shows promise as a therapeutic strategy to hasten wound maturity.
Okwueze
Martina I
MI
Department of Plastic Surgery, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA.
Cardwell
Nancy L
NL
Pollins
Alonda C
AC
Nanney
Lillian B
LB
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002197:Capillary Action; D049109:Cell Proliferation; D004815:Epidermal Growth Factor / Q000235:genetics / Q000502:physiology*; D066260:Epiregulin; D005786:Gene Expression Regulation / Q000502:physiology; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D015603:Keratinocytes / Q000502:physiology; D023421:Models, Animal; D020893:Receptor, ErbB-3 / Q000235:genetics / Q000502:physiology*; D012867:Skin / Q000098:blood supply / Q000293:injuries / Q000503:physiopathology; D013552:Swine; D014162:Transfection; D014945:Wound Healing / Q000235:genetics / Q000502:physiology*
C587880:EREG protein, human; D066260:Epiregulin; C587883:HBEGF protein, human; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D004815:Epidermal Growth Factor; D020893:Receptor, ErbB-3