Recombinant FGF21 Protects Against Blood-Brain Barrier Leakage Through Nrf2 Upregulation in Type 2 Diabetes Mice

doi:10.1007/s12035-018-1234-2

科研成果详情

题名	Recombinant FGF21 Protects Against Blood-Brain Barrier Leakage Through Nrf2 Upregulation in Type 2 Diabetes Mice
作者	Yu, Zhanyang 1; Lin, Li2; Jiang, Yinghua 1; Chin, Ian 1; Wang, Xiaojie 2; Li, Xiaokun2; Lo, Eng H.1; Wang, Xiaoying 1
发表日期	2019-04
发表期刊	MOLECULAR NEUROBIOLOGY 影响因子和分区
语种	英语
原始文献类型	Article
关键词	Fibroblast growth factor 21 (FGF21) Diabetes Blood-brain barrier (BBB) Hyperglycemia Inflammation FGFR1 Nrf2 Keap1
其他关键词	GENE-EXPRESSION ; PERMEABILITY ; INJURY ; HYPERGLYCEMIA ; INFLAMMATION ; STRESS ; CELLS ; KEAP1
摘要	Blood-brain barrier (BBB) damage is a characteristic feature of diabetes mellitus pathology and plays significant roles in diabetes-associated neurological disorders. However, effective treatments for diabetes targeting BBB damage are yet to be developed. Fibroblast growth factor 21 (FGF21) is a potent regulator of lipid and glucose metabolism. In this study, we tested the hypothesis that recombinant FGF21 (rFGF21) administration may reduce type 2 diabetes (T2D)-induced BBB disruption via NF-E2-related factor-2 (Nrf2) upregulation. Our experimental results show that rFGF21 treatment significantly ameliorated BBB permeability and preserved junction protein expression in db/db mice in vivo. This protective effect was further confirmed by ameliorated transendothelial permeability and junction protein loss by rFGF21 under hyperglycemia and IL1 (HG-IL1) condition in cultured human brain microvascular endothelial cells (HBMEC) in vitro. We further reveal that rFGF21 can activate FGF receptor 1 (FGFR1) that increases its binding with Kelch ECH-associating protein 1 (Keap1), a repressor of Nrf2, thereby reducing Keap1-Nrf2 interaction leading to Nrf2 release. These data suggest that rFGF21 administration may decrease T2D-induced BBB permeability, at least in part via FGFR1-Keap1-Nrf2 activation pathway. This study may provide an impetus for development of therapeutics targeting BBB damage in diabetes.
资助项目	AHA Scientist Development GrantAmerican Heart Association [15SDG25550035]; National Institute of Health (NIH)United States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [5R01NS099539]; NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKEUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Neurological Disorders & Stroke (NINDS) [R01NS099539] Funding Source: NIH RePORTER
出版者	SPRINGER
出版地	NEW YORK
ISSN	0893-7648
EISSN	1559-1182
卷号	56 期号:4 页码:2314-2327
DOI	10.1007/s12035-018-1234-2
页数	14
WOS类目	Neurosciences
WOS研究方向	Neurosciences & Neurology
WOS记录号	WOS:000465498200002
收录类别	SCIE ; PUBMED ; SCOPUS
URL	查看原文
Pubmed记录号	30022432
PMC记录号	PMC6339597
Scopus记录号	2-s2.0-85050196255
ESI高被引论文	2020-01 ; 2020-03
通讯作者地址	[Yu, Zhanyang]Neuroprotection Research Laboratory,Departments of Radiology and Neurology,Massachusetts General Hospital and Harvard Medical School,149 13th Street, Room 2401,Boston,02129,United States
scopus学科分类	Neurology;Cellular and Molecular Neuroscience
引用统计	被引频次：29[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/9016
专题	药学院（分析测试中心）_生物制药系_生物制药工程
通讯作者	Yu, Zhanyang
作者单位	1.Neuroprotection Research Laboratory,Departments of Radiology and Neurology,Massachusetts General Hospital and Harvard Medical School,149 13th Street, Room 2401,Boston,02129,United States; 2.School of Pharmaceutical Sciences,Key Laboratory of Biotechnology and Pharmaceutical Engineering,Wenzhou Medical University,Wenzhou,325035,China
推荐引用方式 GB/T 7714	Yu, Zhanyang,Lin, Li,Jiang, Yinghua,et al. Recombinant FGF21 Protects Against Blood-Brain Barrier Leakage Through Nrf2 Upregulation in Type 2 Diabetes Mice[J]. MOLECULAR NEUROBIOLOGY,2019,56(4):2314-2327.
APA	Yu, Zhanyang., Lin, Li., Jiang, Yinghua., Chin, Ian., Wang, Xiaojie., ... & Wang, Xiaoying. (2019). Recombinant FGF21 Protects Against Blood-Brain Barrier Leakage Through Nrf2 Upregulation in Type 2 Diabetes Mice. MOLECULAR NEUROBIOLOGY, 56(4), 2314-2327.
MLA	Yu, Zhanyang,et al."Recombinant FGF21 Protects Against Blood-Brain Barrier Leakage Through Nrf2 Upregulation in Type 2 Diabetes Mice".MOLECULAR NEUROBIOLOGY 56.4(2019):2314-2327.