Department of Dermatology, USC-Norris Comprehensive Cancer Center, University of Southern California Keck Medical Center , Los Angeles, California, USA.
Department of Surgery, University of Southern California Keck Medical Center , Los Angeles, California, USA.
Mol Ther Methods Clin Dev. 2016 Jun 22;3:16041. doi: 10.1038/mtm.2016.41. eCollection 2016.
Burn injuries are a leading cause of morbidity including prolonged hospitalization, disfigurement, and disability. Currently there is no Food and Drug Administration-approved burn therapeutics. A clinical distinction of burn injuries from other acute wounds is the event of the so-called secondary burn wound progression within the first week of the injury, in which a burn expands horizontally and vertically from its initial boundary to a larger area. Therefore, an effective therapeutics for burns should show dual abilities to prevent the burn wound progression and thereafter promote burn wound healing. Herein we report that topically applied F-5 fragment of heat shock protein-90α is a dual functional agent to promote burn wound healing in pigs. First, F-5 prevents burn wound progression by protecting the surrounding cells from undergoing heat-induced caspase 3 activation and apoptosis with increased Akt activation. Accordingly, F-5-treated burn and excision wounds show a marked decline in inflammation. Thereafter, F-5 accelerates burn wound healing by stimulating the keratinocyte migration-led reepithelialization, leading to wound closure. This study addresses a topical agent that is capable of preventing burn wound progression and accelerating burn wound healing.
烧伤是发病率的主要原因，包括延长住院时间、毁容和残疾。目前，还没有获得美国食品和药物管理局批准的烧伤治疗药物。烧伤与其他急性伤口的临床区别在于，在受伤后的第一周内会发生所谓的二次烧伤进展，烧伤会从初始边界向更大的区域水平和垂直扩展。因此，有效的烧伤治疗药物应该具有双重能力，既能防止烧伤创面进展，又能促进烧伤创面愈合。在此，我们报告热休克蛋白 90α 的 F-5 片段是一种促进猪烧伤创面愈合的双重功能药物。首先，F-5 通过增加 Akt 的激活来保护周围细胞免受热诱导的半胱天冬酶 3 激活和细胞凋亡，从而防止烧伤创面进展。因此，F-5 处理的烧伤和切除伤口的炎症明显减少。此后，F-5 通过刺激角质形成细胞迁移促进再上皮化，加速烧伤创面愈合，从而实现创面闭合。本研究提出了一种能够防止烧伤创面进展和加速烧伤创面愈合的局部治疗药物。
