title: Impaired wound healing results from the dysfunction of the Akt/mTOR pathway in diabetic rats.
abstract: BACKGROUND
  Wound healing is impaired in diabetes mellitus. The underlying mechanism involved in this process is still unknown. The Akt/mTOR signaling pathway plays a crucial role in the pathogenesis of diabetes.
  
  
  OBJECTIVE
  we investigated the role of the Akt/mTOR pathway in diabetic wounds and the mechanisms that growth factors activate this pathway to promote diabetic wound healing.
  
  
  METHODS
  Full-thickness skin excisional wounds were created on the backs of normal and streptozotocin-induced diabetic rats. The expression of key proteins in the Akt/mTOR pathway was assayed using western blotting; topical effects of granulocyte-macrophage colony stimulating factor (GM-CSF) on diabetic wounds and activation of the Akt/mTOR pathway were subsequently investigated. Activation of the Akt/mTOR pathway by GM-SCF in vitro was examined in rat primary fibroblasts.
  
  
  RESULTS
  The results indicate that the Akt/mTOR pathway was activated in the wound tissue of both non-diabetic and diabetic rats, as indicated by a remarkable increase in expression of total and phosphorylated key proteins in this pathway. However, the expression level of these proteins was dramatically attenuated in diabetic wounds compared with non-diabetic wounds. Upon topical application of GM-CSF, the diabetic wound healing was remarkably improved concomitantly with increased expression and phosphorylation of key proteins in the Akt/mTOR pathway. In addition, rat fibroblast proliferation induced by GM-CSF depended on the Akt/mTOR pathway activation.
  
  
  CONCLUSIONS
  Impaired wound healing results from the dysfunction of the Akt/mTOR pathway in diabetic rats. The pharmacologic elevation of this pathway may represent an attractive intervention strategy to improve prognosis of diabetic wounds.
authors.affiliation: State Key Laboratory of Trauma, Burns and Combined Injury, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing 400042, China; Cell-Based Therapy Center, Daping Hospital, Third Military Medical University, Chongqing 400042, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Huang
authors.affiliation: China Hai Yang Ren Min Hospital, No. 73. Haiyang District, Haiyang, Shandong Province, China.
authors.forename: Wenhui
authors.initials: W
authors.lastname: Cui
authors.affiliation: State Key Laboratory of Trauma, Burns and Combined Injury, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing 400042, China; Department of Dermatology, The First Affiliated Hospital of Wenzhou Medical University, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Qiu
authors.affiliation: State Key Laboratory of Trauma, Burns and Combined Injury, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing 400042, China; Cell-Based Therapy Center, 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, Burns and Combined Injury, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing 400042, China; Cell-Based Therapy Center, Daping Hospital, Third Military Medical University, Chongqing 400042, China.
authors.forename: Rongshen
authors.initials: R
authors.lastname: Zhao
authors.affiliation: State Key Laboratory of Trauma, Burns and Combined Injury, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing 400042, China.
authors.forename: Dengfen
authors.initials: D
authors.lastname: Zeng
authors.affiliation: State Key Laboratory of Trauma, Burns and Combined Injury, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing 400042, China; Cell-Based Therapy Center, Daping Hospital, Third Military Medical University, Chongqing 400042, China.
authors.forename: Chenhui
authors.initials: C
authors.lastname: Dong
authors.affiliation: State Key Laboratory of Trauma, Burns and Combined Injury, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing 400042, China.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Trauma, Burns and Combined Injury, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing 400042, China; Cell-Based Therapy Center, 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, Burns and Combined Injury, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing 400042, China; Cell-Based Therapy Center, 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, Burns and Combined Injury, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing 400042, China; Cell-Based Therapy Center, Daping Hospital, Third Military Medical University, Chongqing 400042, China.
authors.forename: Xiangyun
authors.initials: X
authors.lastname: Li
authors.affiliation: State Key Laboratory of Trauma, Burns and Combined Injury, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing 400042, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Li
authors.affiliation: State Key Laboratory of Trauma, Burns and Combined Injury, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing 400042, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Tan
authors.affiliation: State Key Laboratory of Trauma, Burns and Combined Injury, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing 400042, China.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Trauma, Burns and Combined Injury, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing 400042, China.
authors.forename: Lizhao
authors.initials: L
authors.lastname: Chen
authors.affiliation: Institute of Basic Medical Science, PLA General Hospital, Beijing 100853, China.
authors.forename: Xiaobing
authors.initials: X
authors.lastname: Fu
authors.affiliation: Department of General Surgery, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing 400042, China. Electronic address: ldl1967@sina.com.
authors.forename: Donglin
authors.initials: D
authors.lastname: Luo
authors.affiliation: State Key Laboratory of Trauma, Burns and Combined Injury, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing 400042, China; Cell-Based Therapy Center, 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: D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism* / Q000503:physiopathology; D039561:Eukaryotic Initiation Factor-4E / Q000378:metabolism; D039562:Eukaryotic Initiation Factor-4F / Q000378:metabolism; D039603:Eukaryotic Initiation Factor-4G / Q000378:metabolism; D005347:Fibroblasts; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D061251:Primary Cell Culture; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism; D015398:Signal Transduction; D012879:Skin Physiological Phenomena; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D014746:Vimentin / Q000378:metabolism; D014945:Wound Healing / Q000187:drug effects
chemical_list: D002352:Carrier Proteins; C499526:Eif4ebp1 protein, rat; D039561:Eukaryotic Initiation Factor-4E; D039562:Eukaryotic Initiation Factor-4F; D039603:Eukaryotic Initiation Factor-4G; D047908:Intracellular Signaling Peptides and Proteins; D010750:Phosphoproteins; D014746:Vimentin; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; C546845:mTOR protein, rat; D051057:Proto-Oncogene Proteins c-akt; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D058570:TOR Serine-Threonine Kinases
keywords: Diabetic rats; Fibroblast; Granulocyte-macrophage colony-stimulating factor; Streptozotocin; The Akt/mTOR pathway; Wound healing