Wei Xing1, Wei Guo1, Cun-Hua Zou1, Ting-Ting Fu1, Xiang-Yun Li1, Ming Zhu1, Jun-Hua Qi1, Jiao Song1, Chen-Hui Dong1, Zhuang Li1, Yong Xiao1, Pei-Song Yuan1, Hong Huang2, Xiang Xu3. 1. State Key Laboratory of Trauma, Burn and Combined Injury, Research Institute of Surgery and Daping Hospital, Third Military Medical University, Chongqing 400042, China. 2. State Key Laboratory of Trauma, Burn and Combined Injury, Research Institute of Surgery and Daping Hospital, Third Military Medical University, Chongqing 400042, China. Electronic address: honghcq@hotmail.com. 3. State Key Laboratory of Trauma, Burn and Combined Injury, Research Institute of Surgery and Daping Hospital, Third Military Medical University, Chongqing 400042, China. Electronic address: Xiangxu@ymail.com.
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.
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.
Authors: Stefania Vitale; Sara Colanero; Martina Placidi; Giovanna Di Emidio; Carla Tatone; Fernanda Amicarelli; Anna Maria D'Alessandro Journal: Molecules Date: 2022-06-01 Impact factor: 4.927
Authors: Mariáurea M Sarandy; Rômulo D Novaes; Antônio A Xavier; Camilo E Vital; João P V Leite; Fabiana C S A Melo; Reggiani V Gonçalves Journal: Biomed Res Int Date: 2017-09-13 Impact factor: 3.411