aFGF alleviates diabetic endothelial dysfunction by decreasing oxidative stress via Wnt/beta-catenin-mediated upregulation of HXK2

doi:10.1016/j.redox.2020.101811

科研成果详情

题名	aFGF alleviates diabetic endothelial dysfunction by decreasing oxidative stress via Wnt/beta-catenin-mediated upregulation of HXK2
作者	Sun, Jia 1; Huang, Xiaozhong2; Niu, Chao3; Wang, Xuejiao 4; Li, Wanqian 1; Liu, Mengxue4; Wang, Ying 5; Huang, Shuai 6; Chen, Xixi 7; Li, Xiaokun1; Wang, Yang4; Jin, Litai1; Xiao, Jian1; Cong, Weitao1
发表日期	2021-02
发表期刊	REDOX BIOLOGY 影响因子和分区
语种	英语
原始文献类型	Article
关键词	aFGF Diabetes Endothelial dysfunction Mitochondrial superoxide HXK2
其他关键词	MITOCHONDRIAL SUPEROXIDE ; VASCULAR DYSFUNCTION ; GROWTH-FACTORS ; CELLS ; INHIBITION ; BINDING ; CANCER ; DNA
摘要	Vascular complications of diabetes are a serious challenge in clinical practice, and effective treatments are an unmet clinical need. Acidic fibroblast growth factor (aFGF) has potent anti-oxidative properties and therefore has become a research focus for the treatment of diabetic vascular complications. However, the specific mechanisms by which aFGF regulates these processes remain unclear. The purpose of this study was to investigate whether aFGF alleviates diabetic endothelial dysfunction by suppressing mitochondrial oxidative stress. We found that aFGF markedly decreased mitochondrial superoxide generation in both db/db mice and endothelial cells incubated with high glucose (30 mM) plus palmitic acid (PA, 0.1 mM), and restored diabetes-impaired Wnt/p-catenin signaling. Pretreatment with the Wnt/beta-catenin signaling inhibitors IWR-1-endo (IWR) and ICG-001 abolished aFGF-mediated attenuation of mitochondrial superoxide generation and endothelial protection. Furthermore, the effects of aFGF on endothelial protection under diabetic conditions were suppressed by c-Myc knockdown. Mechanistically, c-Myc knockdown triggered mitochondrial superoxide generation, which was related to decreased expression and subsequent impaired mitochondrial localization of hexokinase 2 (HXK2). The role of HXK2 in aFGF-mediated attenuation of mitochondrial superoxide levels and EC protection was further confirmed by si-Hxk2 and a cell-permeable form of hexokinase II VDAC binding domain (HXK2VBD) peptide, which inhibits mitochondrial localization of HXK2. Taken together, these findings suggest that the endothelial protective effect of aFGF under diabetic conditions could be partly attributed to its role in suppressing mitochondrial superoxide generation via HXK2, which is mediated by the Wnt/beta-catenin/c-Myc axis.
资助项目	National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81903235, 81870209, 81773346, 81770498, 82070507]; Key Scientific Project of MOST, China [2017YFA0506000]; Natural Science Foundation of Zhejiang ProvinceNatural Science Foundation of Zhejiang Province [LQ18H020004, Y21H020057]; Zhejiang Province Medical and Health Science Program [2019KY099, 2019RC054]; Wenzhou Science and Technology Bureau Foundation [Y20180145, Y20190164]
出版者	ELSEVIER
出版地	AMSTERDAM
ISSN	2213-2317
卷号	39 页码:101811
DOI	10.1016/j.redox.2020.101811
页数	16
WOS类目	Biochemistry & Molecular Biology
WOS研究方向	Biochemistry & Molecular Biology
WOS记录号	WOS:000608820500004
收录类别	SCIE ; PUBMED ; SCOPUS
URL	查看原文
PubMed ID	33360774
PMC记录号	PMC7772795
SCOPUSEID	2-s2.0-85098220632
通讯作者地址	[Cong, Weitao]School of Pharmaceutical Science,Wenzhou Medical University,Wenzhou,China ; [Wang, Yang]Department of Histology and Embryology,Institute of Neuroscience,Wenzhou Medical University,Wenzhou,325000,China ; [Jin, Litai]School of Pharmaceutical Science,Wenzhou Medical University,Wenzhou,China ; [Xiao, Jian]School of Pharmaceutical Science,Wenzhou Medical University,Wenzhou,China
Scopus学科分类	Organic Chemistry
引用统计	被引频次：12[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/5376
专题	药学院（分析测试中心）附属第二医院附属第一医院第二临床医学院、附属第二医院、育英儿童医院研究生工作部（研究生院）基础医学院（机能实验教学中心）_形态学系_组织胚胎学
通讯作者	Wang, Yang; Jin, Litai; Xiao, Jian; Cong, Weitao
作者单位	1.School of Pharmaceutical Science,Wenzhou Medical University,Wenzhou,China; 2.Department of Pediatric Surgery,The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University,Wenzhou,China; 3.Pediatric Research Institute,The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University,Wenzhou,China; 4.Department of Histology and Embryology,Institute of Neuroscience,Wenzhou Medical University,Wenzhou,325000,China; 5.Department of Pharmacy,Jinhua Women & Children Health Hospital,Jinhua,China; 6.Zhejiang Provincial Key Laboratory of Interventional Pulmonology,The First Affiliated Hospital of Wenzhou Medical University,Wenzhou,China; 7.Department of Pharmacy,Taizhou Central Hospital (Taizhou University Hospital),Taizhou,China
第一作者单位	温州医科大学
通讯作者单位	温州医科大学; 组织胚胎学
第一作者的第一单位	温州医科大学
推荐引用方式 GB/T 7714	Sun, Jia,Huang, Xiaozhong,Niu, Chao,et al. aFGF alleviates diabetic endothelial dysfunction by decreasing oxidative stress via Wnt/beta-catenin-mediated upregulation of HXK2[J]. REDOX BIOLOGY,2021,39:101811.
APA	Sun, Jia., Huang, Xiaozhong., Niu, Chao., Wang, Xuejiao., Li, Wanqian., ... & Cong, Weitao. (2021). aFGF alleviates diabetic endothelial dysfunction by decreasing oxidative stress via Wnt/beta-catenin-mediated upregulation of HXK2. REDOX BIOLOGY, 39, 101811.
MLA	Sun, Jia,et al."aFGF alleviates diabetic endothelial dysfunction by decreasing oxidative stress via Wnt/beta-catenin-mediated upregulation of HXK2".REDOX BIOLOGY 39(2021):101811.