Giles Natalie, Rea Suzanne, Beer Trevor, Wood Fiona M, Fear Mark W
The McComb Foundation, University of Western Australia, Perth, WA, Australia.
Wound Repair Regen. 2008 Jan-Feb;16(1):58-64. doi: 10.1111/j.1524-475X.2007.00331.x.
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.
在移除热原后，烧伤创面周围的组织会受到严重损伤。这种损伤是由淤滞区内坏死性和凋亡性细胞死亡共同作用引起的。保留淤滞区可以减小创面大小，从而促进伤口愈合。我们测试了一种先前被鉴定为通过抑制c-Jun来抑制神经元坏死性和凋亡性细胞死亡的肽是否能促进伤口愈合。我们首先在培养的角质形成细胞和成纤维细胞系中测试了这种肽的作用。该肽促进了角质形成细胞的增殖，但对成纤维细胞的增殖没有影响，同时该肽还抑制了紫外线诱导的角质形成细胞凋亡。我们最终在烧伤小鼠模型中对该肽进行了体内测试。用该肽处理的伤口比对照伤口更快地重新上皮化，并且在受伤后24小时，伤口部位周围的细胞死亡明显减少，这表明该肽对凋亡的预防作用及其增殖作用都有助于伤口愈合过程。我们的数据表明c-Jun在伤口修复的多个过程中起作用，并证明在受伤时使用c-Jun二聚化抑制剂治疗烧伤可以促进伤口愈合。
