Xing Wei, Guo Wei, Zou Cun-Hua, Fu Ting-Ting, Li Xiang-Yun, Zhu Ming, Qi Jun-Hua, Song Jiao, Dong Chen-Hui, Li Zhuang, Xiao Yong, Yuan Pei-Song, Huang Hong, Xu Xiang
State Key Laboratory of Trauma, Burn and Combined Injury, Research Institute of Surgery and Daping Hospital, Third Military Medical University, Chongqing 400042, China.
State Key Laboratory of Trauma, Burn and Combined Injury, Research Institute of Surgery and Daping Hospital, Third Military Medical University, Chongqing 400042, China.
J Dermatol Sci. 2015 Aug;79(2):101-9. doi: 10.1016/j.jdermsci.2015.03.016. Epub 2015 Apr 1.
Acemannan is a bioactive polysaccharides promoting tissue repair. However, the roles of acemannan in skin wound healing and the underlying molecular mechanisms are largely unclear.
The goal of this study is to investigate the positive role of acemannan in cutaneous wound healing and its mechanism.
Mouse skin wound model and skin primary fibroblasts were used to demonstrate the positive effect of acemannan on cutaneous wound healing. The expressions of cell proliferation nuclear antigen ki-67, cyclin D1 and activity of AKT/mTOR signaling were analyzed in acemannan-treated fibroblasts and mice. Rapamycin and AKT inhibitor VIII were used to determine the key role of AKT/mTOR signaling in acemannan-promoting cutaneous wound healing.
We found that acemannan significantly accelerated skin wound closure and cell proliferation. Acemannan promoted the expression of cyclin D1 in cultured fibroblasts, which was mediated by AKT/mTOR signal pathway leading to enhanced activity of the eukaryotic translation initiation factor-4F (eIF4F) and increased translation of cyclin D1. In contrast, pharmaceutical blockade of AKT/mTOR signaling by mTOR inhibitor rapamycin or AKT inhibitor VIII abolished acemannan-induced cyclin D1 translation and cell proliferation. In vivo studies confirmed that the activation of AKT/mTOR by acemannan played a key role in wound healing, which could be reversed by rapamycin.
Acemannan promoted skin wound healing partly through activating AKT/mTOR-mediated protein translation mechanism, which may represent an alternative therapy approach for cutaneous wound.
乙酰甘露聚糖是一种促进组织修复的生物活性多糖。然而，乙酰甘露聚糖在皮肤伤口愈合中的作用及其潜在分子机制尚不清楚。
本研究旨在探讨乙酰甘露聚糖在皮肤伤口愈合中的积极作用及其机制。
采用小鼠皮肤伤口模型和皮肤原代成纤维细胞来证明乙酰甘露聚糖对皮肤伤口愈合的积极作用。分析乙酰甘露聚糖处理的成纤维细胞和小鼠中细胞增殖核抗原ki-67、细胞周期蛋白D1的表达以及AKT/mTOR信号通路的活性。使用雷帕霉素和AKT抑制剂VIII来确定AKT/mTOR信号通路在乙酰甘露聚糖促进皮肤伤口愈合中的关键作用。
我们发现乙酰甘露聚糖显著加速皮肤伤口闭合和细胞增殖。乙酰甘露聚糖促进培养的成纤维细胞中细胞周期蛋白D1的表达，这是由AKT/mTOR信号通路介导的，导致真核翻译起始因子-4F（eIF4F）活性增强，细胞周期蛋白D1的翻译增加。相反，mTOR抑制剂雷帕霉素或AKT抑制剂VIII对AKT/mTOR信号通路的药物阻断消除了乙酰甘露聚糖诱导的细胞周期蛋白D1翻译和细胞增殖。体内研究证实，乙酰甘露聚糖对AKT/mTOR的激活在伤口愈合中起关键作用，雷帕霉素可使其逆转。
乙酰甘露聚糖部分通过激活AKT/mTOR介导的蛋白质翻译机制促进皮肤伤口愈合，这可能代表一种治疗皮肤伤口的替代方法。
