title: Acemannan accelerates cell proliferation and skin wound healing through AKT/mTOR signaling pathway.
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.
  
  
  CONCLUSIONS
  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.affiliation: State Key Laboratory of Trauma, Burn and Combined Injury, Research Institute of Surgery and Daping Hospital, Third Military Medical University, Chongqing 400042, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Xing
authors.affiliation: State Key Laboratory of Trauma, Burn and Combined Injury, Research Institute of Surgery and Daping Hospital, Third Military Medical University, Chongqing 400042, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Guo
authors.affiliation: State Key Laboratory of Trauma, Burn and Combined Injury, Research Institute of Surgery and Daping Hospital, Third Military Medical University, Chongqing 400042, China.
authors.forename: Cun-Hua
authors.initials: CH
authors.lastname: Zou
authors.affiliation: State Key Laboratory of Trauma, Burn and Combined Injury, Research Institute of Surgery and Daping Hospital, Third Military Medical University, Chongqing 400042, China.
authors.forename: Ting-Ting
authors.initials: TT
authors.lastname: Fu
authors.affiliation: State Key Laboratory of Trauma, Burn and Combined Injury, Research Institute of Surgery and Daping Hospital, Third Military Medical University, Chongqing 400042, China.
authors.forename: Xiang-Yun
authors.initials: XY
authors.lastname: Li
authors.affiliation: State Key Laboratory of Trauma, Burn and Combined Injury, Research Institute of Surgery and Daping Hospital, Third Military Medical University, Chongqing 400042, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Zhu
authors.affiliation: State Key Laboratory of Trauma, Burn and Combined Injury, Research Institute of Surgery and Daping Hospital, Third Military Medical University, Chongqing 400042, China.
authors.forename: Jun-Hua
authors.initials: JH
authors.lastname: Qi
authors.affiliation: State Key Laboratory of Trauma, Burn and Combined Injury, Research Institute of Surgery and Daping Hospital, Third Military Medical University, Chongqing 400042, China.
authors.forename: Jiao
authors.initials: J
authors.lastname: Song
authors.affiliation: State Key Laboratory of Trauma, Burn and Combined Injury, Research Institute of Surgery and Daping Hospital, Third Military Medical University, Chongqing 400042, China.
authors.forename: Chen-Hui
authors.initials: CH
authors.lastname: Dong
authors.affiliation: State Key Laboratory of Trauma, Burn and Combined Injury, Research Institute of Surgery and Daping Hospital, Third Military Medical University, Chongqing 400042, China.
authors.forename: Zhuang
authors.initials: Z
authors.lastname: Li
authors.affiliation: State Key Laboratory of Trauma, Burn and Combined Injury, Research Institute of Surgery and Daping Hospital, Third Military Medical University, Chongqing 400042, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Xiao
authors.affiliation: State Key Laboratory of Trauma, Burn and Combined Injury, Research Institute of Surgery and Daping Hospital, Third Military Medical University, Chongqing 400042, China.
authors.forename: Pei-Song
authors.initials: PS
authors.lastname: Yuan
authors.affiliation: 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.
authors.forename: Hong
authors.initials: H
authors.lastname: Huang
authors.affiliation: 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.
authors.forename: Xiang
authors.initials: X
authors.lastname: Xu
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D019938:Cyclin D1 / Q000378:metabolism; D008297:Male; D008351:Mannans / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D023421:Models, Animal; D051058:Oncogene Protein v-akt / Q000378:metabolism*; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D000276:Adjuvants, Immunologic; C530105:Ccnd1 protein, mouse; D008351:Mannans; D019938:Cyclin D1; C546843:mTOR protein, mouse; D051058:Oncogene Protein v-akt; D058570:TOR Serine-Threonine Kinases; C058414:acemannan
keywords: AKT; Acemannan; Cyclin D1; Wound healing; mTOR