Zhang Yue, Bai Xiaozhi, Wang Yunchuan, Li Na, Li Xiaoqiang, Han Fei, Su Linlin, Hu Dahai
Department of Burns and Cutaneous Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, Shannxi, China.
PLoS One. 2014 Aug 11;9(8):e103723. doi: 10.1371/journal.pone.0103723. eCollection 2014.
Inflammation, proliferation, and tissue remodeling are essential steps for wound healing. The hypoxic wound microenvironment promotes cell migration through a hypoxia--heat shock protein 90 alpha (Hsp90α)--low density lipoprotein receptor-related protein-1 (LRP-1) autocrine loop. To elucidate the role of this autocrine loop on burn wound healing, we investigated the expression profile of Hsp90α at the edge of burn wounds and found a transient increase in both mRNA and protein levels. Experiments performed with a human keratinocyte cell line--HaCaT also confirmed above results. 17-dimethylaminoethylamino-17demethoxygeldanamycin hydrochloride (17-DMAG), an Hsp90α inhibitor, was used to further evaluate the function of Hsp90α in wound healing. Consistently, topical application of Hsp90α in the early stage of deep second-degree burn wounds led to reduced inflammation and increased tissue granulation, with a concomitant reduction in the size of the wound at each time point tested (p<0.05). Consequently, epidermal cells at the wound margin progressed more rapidly causing an expedited healing process. In conclusion, these results provided a rationale for the therapeutic effect of Hsp90α on the burn wound management.
炎症、增殖和组织重塑是伤口愈合的关键步骤。缺氧的伤口微环境通过缺氧-热休克蛋白90α（Hsp90α）-低密度脂蛋白受体相关蛋白1（LRP-1）自分泌环促进细胞迁移。为了阐明这种自分泌环在烧伤创面愈合中的作用，我们研究了烧伤创面边缘Hsp90α的表达谱，发现mRNA和蛋白水平均有短暂升高。用人角质形成细胞系HaCaT进行的实验也证实了上述结果。17-二甲基氨基乙基氨基-17-去甲氧基格尔德霉素盐酸盐（17-DMAG），一种Hsp90α抑制剂，被用于进一步评估Hsp90α在伤口愈合中的功能。同样，在深二度烧伤创面早期局部应用Hsp90α可减轻炎症并增加组织肉芽形成，在每个测试时间点伤口大小均随之减小（p<0.05）。因此，伤口边缘的表皮细胞进展更快，导致愈合过程加快。总之，这些结果为Hsp90α在烧伤创面处理中的治疗作用提供了理论依据。
