A peptide inhibitor of c-Jun promotes wound healing in a mouse full-thickness burn model.
Significant damage to tissue surrounding burn injuries occurs after the removal of the thermal source. This damage is caused by a combination of both necrotic and apoptotic cell death in the zone of stasis. Preserving the zone of stasis can reduce the wound size and thereby improve wound healing. We tested whether a peptide previously identified to inhibit necrotic and apoptotic cell death in neurons through c-Jun inhibition could enhance wound healing. We first tested the effects of this peptide on a keratinocyte and fibroblast cell line in culture. The peptide promoted proliferation of keratinocytes but had no effect on fibroblast proliferation, while the peptide also inhibited ultraviolet-induced apoptosis of keratinocytes. We finally tested the peptide in vivo, using a mouse model of burn injury. Wounds that were treated with the peptide reepithelialized faster than controls, while cell death surrounding the wound site was markedly reduced 24 hours postinjury, suggesting that the prevention of apoptosis as well as the proliferative effects of this peptide contribute to the wound healing process. Our data implicate c-Jun in multiple processes during wound repair and demonstrate that treatment of burn injuries using inhibitors of c-Jun dimerization at the time of injury can promote wound healing.
Giles
Natalie
N
The McComb Foundation, University of Western Australia, Perth, WA, Australia.
Rea
Suzanne
S
Beer
Trevor
T
Wood
Fiona M
FM
Fear
Mark W
MW
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002056:Burns / Q000188:drug therapy*; D049109:Cell Proliferation / Q000187:drug effects; D019281:Dimerization; D004195:Disease Models, Animal; D015603:Keratinocytes / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D010455:Peptides / Q000494:pharmacology*; D016755:Proto-Oncogene Proteins c-jun / Q000037:antagonists & inhibitors*; D014945:Wound Healing / Q000187:drug effects*
D010455:Peptides; D016755:Proto-Oncogene Proteins c-jun