Effects of FOXO1 mediated regulation of mitochondrial function in diabetic wound healing

作     者：SHI Yun-di WANG Di LI Xue-jun TIE Lu 

作者机构：State Key Laboratory of Natural & Biomimetic DrugsDepartment of PharmacologySchool of Basic Medical Sciencesand Institute of System BiomedicinePeking University 

出 版 物：《中国药理学与毒理学杂志》 (Chinese Journal of Pharmacology and Toxicology)

年 卷 期：2016年第30卷第10期

页      面：1050-1050页

核心收录：

学科分类：1002[医学-临床医学] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 10[医学] 

基　　金：The project supported by National Natural Science Foundation of China(81373405,30901803) Beijing Higher Education Young Elite Teacher Project(YETP0053) 

主　　题：diabetes FOXO1 endothelial mitochondrial fission 

摘      要：OBJECTIVE Refractory wounds in diabetic patients constitute a serious complication that often leads to amputation with limited treatment *** studies have shown that the imbalance of mitochondrial dynamics was associated with the increased reactive oxygen species(ROS)production in endothelial cells,which is a significant contributor to the microvascular complications of *** present study was designed to determine the involvement of transcription factor FOXO1in diabetic wound healing and investigate underlying ***&RESULTS Impaired mitochondrial networks and increased phosphorylation of dynaminrelated protein-1(Drp1)at ser616,a protein required for mitochondrial fission,were observed in human umbilical vein endothelial cells(HUVECs)24 h after exposure to high concentrations of *** of FOXO1 by si RNA or by FOXO1 selective inhibitor AS1842856 abrogated high glucos-induced alterations in mitochondrial networks and phosphorylation of *** with AS1842856 or si RNA of FOXO1 could significantly increase the mitochondrial membrane potential and suppress the overproduction of ROS induced by high *** of AS1842856 inhibited glucoseinduced apoptosis,ameliorated capillary tube formation in *** vivo,AS1842856 dose-dependently rescued the delay of wound closure in diabetic mice,and5 mg·kg-1of AS1842856 treatment significantly increased the mean perfusion *** These findings suggested that FOXO1 is critical to preserve mitochondrial quantity and function in endothelial cells,inhibition of FOXO1 rescued the delayed wound healing and improved wound angiogenesis in diabetic mice.