Impaired wound healing results from the dysfunction of the Akt/mTOR pathway in diabetic rats

• DOI: 10.1016/j.jdermsci.2015.06.002
• Publication Date: 2015-06-13T02:54:50Z
• Authors: Hong Huang; Wenhui Cui; Wei Qiu; Ming Zhu; Rongshen Zhao; Dengfen Zeng; Chenhui Dong; Xiaohui Wang; Wei Guo; Wei Xing; Xiangyun Li; Lei Li; Yan Tan; Xiaofeng Wu; Lizhao Chen; Xiaobing Fu; Donglin Luo; Xiang Xu
• Keywords: Male; 0301 basic medicine; Primary Cell Culture; Intracellular Signaling Peptides and Proteins; Granulocyte-Macrophage Colony-Stimulating Factor; Ribosomal Protein S6 Kinases, 70-kDa; Fibroblasts; Phosphoproteins; Diabetes Mellitus, Experimental; Rats; 3. Good health; Rats, Sprague-Dawley; 03 medical and health sciences; Eukaryotic Initiation Factor-4E; Eukaryotic Initiation Factor-4F; Animals; Phosphorylation; Carrier Proteins; Eukaryotic Initiation Factor-4G; Proto-Oncogene Proteins c-akt; Cells, Cultured; Cell Proliferation; Signal Transduction

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.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.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.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.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.