Acemannan accelerates cell proliferation and skin wound healing through AKT/mTOR signaling pathway. Issue 2 (August 2015)

• Record Type: Journal Article
• Authors: 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
• Is Part Of: Journal of dermatological science. Volume 79:Issue 2(2015:Aug.)
• Page Start: 101
• Page End: 109
• Publication Date: 2015-08
• Subjects: Acemannan -- Wound healing -- AKT -- mTOR -- Cyclin D1; Dermatology -- Periodicals; Skin Diseases -- Periodicals; Dermatologie -- Périodiques; 616.5005
• DOI: 10.1016/j.jdermsci.2015.03.016
• Languages: English
• ISSNs: 0923-1811

Abstract

Highlights: Acemannan promotes skin wound healing and cell proliferation in vivo. Acemannan promotes cell proliferation by inducing cyclin D1 protein translation. Acemannan promotes cyclin D1 protein translation by Akt/mTOR signaling. Acemannan promotes fibroblasts proliferation by activation of Akt/mTOR signaling. Acemannan promotes skin wound healing by activation of mTOR signaling. Abstract: Background: 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. Objective: The goal of this study is to investigate the positive role of acemannan in cutaneous wound healing and its mechanism. Methods: 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. Results: 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. Conclusion: Acemannan promoted skin wound healing partly through activating AKT/mTOR-mediated protein translation mechanism, which may represent an alternative therapy approach for cutaneous wound.