Hong Huang1, Wenhui Cui2, Wei Qiu3, Ming Zhu1, Rongshen Zhao1, Dengfen Zeng4, Chenhui Dong1, Xiaohui Wang4, Wei Guo1, Wei Xing1, Xiangyun Li1, Lei Li4, Yan Tan4, Xiaofeng Wu4, Lizhao Chen4, Xiaobing Fu5, Donglin Luo6, Xiang Xu7. 1. 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. 2. China Hai Yang Ren Min Hospital, No. 73. Haiyang District, Haiyang, Shandong Province, China. 3. 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. 4. State Key Laboratory of Trauma, Burns and Combined Injury, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing 400042, China. 5. Institute of Basic Medical Science, PLA General Hospital, Beijing 100853, China. 6. Department of General Surgery, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing 400042, China. Electronic address: ldl1967@sina.com. 7. 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.
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. CONCLUSION: 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.
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 diabeticrats. 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 diabeticrats, 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. CONCLUSION: Impaired wound healing results from the dysfunction of the Akt/mTOR pathway in diabeticrats. The pharmacologic elevation of this pathway may represent an attractive intervention strategy to improve prognosis of diabetic wounds.
Authors: Anna Luan; Michael S Hu; Tripp Leavitt; Elizabeth A Brett; Kevin C Wang; Michael T Longaker; Derrick C Wan Journal: Adv Wound Care (New Rochelle) Date: 2018-01-01 Impact factor: 4.730
Authors: Mariana Barreto Serra; Wermerson Assunção Barroso; Neemias Neves da Silva; Selma do Nascimento Silva; Antonio Carlos Romão Borges; Iracelle Carvalho Abreu; Marilene Oliveira da Rocha Borges Journal: Int J Inflam Date: 2017-07-25