Up-regulation of Nrf2 is involved in FGF21-mediated fenofibrate protection against type 1 diabetic nephropathy

doi:10.1016/j.freeradbiomed.2016.02.002

科研成果详情

题名	Up-regulation of Nrf2 is involved in FGF21-mediated fenofibrate protection against type 1 diabetic nephropathy
作者	Cheng, Yanli 1,2,3; Zhang, Jingjing 3,4,5; Guo, Weiying 1; Li, Fengsheng 6; Sun, Weixia 1; Chen, Jing 3; Zhang, Chi 2,7; Lu, Xuemian7; Tan, Yi2,3,7,8; Feng, Wenke 8,9; Fu, Yaowen 1; Liu, Gilbert C.10; Xu, Zhonggao 1; Cai, Lu2,3,7,8
发表日期	2016-04
发表期刊	FREE RADICAL BIOLOGY AND MEDICINE 影响因子和分区
语种	英语
原始文献类型	Article
关键词	Diabetic nephropathy PPAR alpha agonist FGF21 Nrf2 Type 1 diabetes Oxidative stress Antioxidants
其他关键词	GROWTH-FACTOR 21 ; OXIDATIVE STRESS ; BARDOXOLONE METHYL ; PPAR-ALPHA ; CELL-DEATH ; ANTIOXIDANT CAPACITY ; KIDNEY-FUNCTION ; IN-VIVO ; FGF21 ; ACTIVATION
摘要	The lipid lowering medication, fenofibrate (FF), is a peroxisome proliferator-activated receptor-alpha (PPARoc) agonist, possessing beneficial effects for type 2 diabetic nephropathy (DN). We investigated whether FF can prevent the development of type 1 DN, and the underlying mechanisms. Diabetes was induced by a single intraperitoneal injection of streptozotocin in C57BL/6J mice. Mice were treated with oral gavage of FF at 100 mg/kg every other day for 3 and 6 months. Diabetes-induced renal oxidative stress, inflammation, apoptosis, lipid and collagen accumulation, and renal dysfunction were accompanied by significant decrease in PI3K, Alt, and GSK-3 beta phosphorylation as well as an increase in the nuclear accumulation of Fyn [a negative regulator of nuclear factor (erythroid-derived 2)-like 2 (Nrf2)]. All these adverse effects were significantly attenuated by FF treatment. FF also significantly increased fibroblast growth factor 21 (FGF21) expression and enhanced Nrf2 function in diabetic and non-diabetic kidneys. Moreover, FF-induced amelioration of diabetic renal damage, including the stimulation of PI3K/Akt/GSK-3 beta/Fyn pathway and the enhancement of Nrf2 function were abolished in FGF21-null mice, confirming the critical role of FGF21 in FF-induced renal protection. These results suggest for the first time that FF prevents the development of DN via up-regulating FGF21 and stimulating PI3K/Akt/GSK-3 beta/Fyn-mediated activation of the Nrf2 pathway. (C) 2016 Elsevier Inc. All rights reserved.
资助项目	National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81300660, 81202151, 81400725, 81471045, 81270809]; Graduate Innovation Fund of Jilin UniversityJilin University [2015032]; Juvenile Diabetes Research FoundationJuvenile Diabetes Research Foundation [1-INO-2014-122-A-N]; National Institutes of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [1R01DK091338-01A1]; NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASESUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK) [R01DK091338] Funding Source: NIH RePORTER; NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISMUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute on Alcohol Abuse & Alcoholism (NIAAA) [R21AA022416] Funding Source: NIH RePORTER
出版者	ELSEVIER SCIENCE INC
出版地	NEW YORK
ISSN	0891-5849
EISSN	1873-4596
卷号	93 页码:94-109
DOI	10.1016/j.freeradbiomed.2016.02.002
页数	16
WOS类目	Biochemistry & Molecular Biology ; Endocrinology & Metabolism
WOS研究方向	Biochemistry & Molecular Biology ; Endocrinology & Metabolism
WOS记录号	WOS:000371219400010
收录类别	SCIE ; PUBMED ; SCOPUS
URL	查看原文
PubMed ID	26849944
PMC记录号	PMC7446394
SCOPUSEID	2-s2.0-84957536494
通讯作者地址	[Xu, Zhonggao]Department of Nephrology,First Hospital of Jilin University,71 Xinmin Street,Changchun,130021,China
Scopus学科分类	Biochemistry;Physiology (medical)
TOP期刊	TOP期刊
引用统计	被引频次：62[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/11281
专题	温州医科大学其他_附属第三医院（瑞安市人民医院）
通讯作者	Xu, Zhonggao
作者单位	1.First Hospital of Jilin University,Changchun,130021,China; 2.Chinese-American Research Institute for Diabetic Complications,Wenzhou Medical University,Wenzhou,325035,China; 3.Kosair Children's Hospital Research Institute,Department of Pediatrics,University of Louisville,Louisville,40202,United States; 4.Department of Cardiology,First Hospital of China Medical University,Shenyang,110016,China; 5.Department of Cardiology,People's Hospital of Liaoning Province,Shenyang,110016,China; 6.Second Artillery General Hospital,Beijing,100088,China; 7.Third Affiliated Hospital of the Wenzhou Medical University,Ruian,325200,China; 8.Department of Pharmacology and Toxicology,University of Louisville,Louisville,40202,United States; 9.Department of Medicine,University of Louisville,Louisville,40202,United States; 10.Child and Adolescent Health Research Design and Support,University of Louisville,Louisville,40204,United States
第一作者单位	温州医科大学
推荐引用方式 GB/T 7714	Cheng, Yanli,Zhang, Jingjing,Guo, Weiying,et al. Up-regulation of Nrf2 is involved in FGF21-mediated fenofibrate protection against type 1 diabetic nephropathy[J]. FREE RADICAL BIOLOGY AND MEDICINE,2016,93:94-109.
APA	Cheng, Yanli., Zhang, Jingjing., Guo, Weiying., Li, Fengsheng., Sun, Weixia., ... & Cai, Lu. (2016). Up-regulation of Nrf2 is involved in FGF21-mediated fenofibrate protection against type 1 diabetic nephropathy. FREE RADICAL BIOLOGY AND MEDICINE, 93, 94-109.
MLA	Cheng, Yanli,et al."Up-regulation of Nrf2 is involved in FGF21-mediated fenofibrate protection against type 1 diabetic nephropathy".FREE RADICAL BIOLOGY AND MEDICINE 93(2016):94-109.