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

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 pot...

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Vydáno v:	Molecular neurobiology Ročník 56; číslo 4; s. 2314 - 2327
Hlavní autoři:	Yu, Zhanyang, Lin, Li, Jiang, Yinghua, Chin, Ian, Wang, Xiaojie, Li, Xiaokun, Lo, Eng H., Wang, Xiaoying
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	New York Springer US 01.04.2019 Springer Nature B.V
Témata:	Animals Biomedical and Life Sciences Biomedicine Blood-brain barrier Blood-Brain Barrier - drug effects Blood-Brain Barrier - pathology Brain injury Cell Biology Cell Membrane Permeability - drug effects Cells, Cultured Diabetes Diabetes mellitus Diabetes mellitus (non-insulin dependent) Diabetes Mellitus, Experimental - drug therapy Diabetes Mellitus, Experimental - genetics Diabetes Mellitus, Type 2 - drug therapy Diabetes Mellitus, Type 2 - genetics Drug development Endothelial cells Endothelial Cells - drug effects Endothelial Cells - metabolism Fibroblast growth factor receptor 1 Fibroblast Growth Factors - pharmacology Fibroblast Growth Factors - therapeutic use Glucose metabolism Humans Hyperglycemia Hyperglycemia - pathology Interleukin 1 Interleukin-1beta - metabolism Kelch-Like ECH-Associated Protein 1 - metabolism Lipid metabolism Male Membrane permeability Mice Microvasculature Models, Biological Neurobiology Neurological diseases Neurology Neurosciences NF-E2-Related Factor 2 - genetics NF-E2-Related Factor 2 - metabolism Permeability Protein Binding - drug effects Proteins Recombinant Proteins - pharmacology Recombinant Proteins - therapeutic use Signal Transduction - drug effects Up-regulation Up-Regulation - drug effects Hyperglycemia Nrf2 Fibroblast growth factor 21 (FGF21) Blood-brain barrier (BBB) Keap1 Inflammation Diabetes FGFR1
ISSN:	0893-7648, 1559-1182, 1559-1182
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Abstract	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 IL1β (HG-IL1β) 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.
AbstractList	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 IL1β (HG-IL1β) 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. 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 IL1β (HG-IL1β) 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, which is in part via FGFR1-Keap1-Nrf2 activation pathway. This study may provide an impetus for development of therapeutics targeting BBB damage in diabetes. 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 IL1β (HG-IL1β) 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.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 IL1β (HG-IL1β) 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.
Author	Wang, Xiaoying Jiang, Yinghua Yu, Zhanyang Chin, Ian Lin, Li Wang, Xiaojie Li, Xiaokun Lo, Eng H.
AuthorAffiliation	1 Neuroprotection Research Laboratory, Departments of Radiology and Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA (Z. Yu, Yu.Zhanyang@mgh.harvard.edu ; Y. Jiang, YJIANG6@mgh.harvare.edu ; I. Chin, icgitar@gmail.com ; E. Lo, lo@helix.mgh.harvard.edu ; X. Wang, wangxi@helix.mgh.harvard.edu ) 2 School of Pharmaceutical Sciences, Key Laboratory of Biotechnology and Pharmaceutical Engineering, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China (L. Lin, linliwz@hotmail.com ; X. Wang, wangxiaojie1972@hotmail.com ; X. Li, xiaokunli@163.net )
AuthorAffiliation_xml	– name: 1 Neuroprotection Research Laboratory, Departments of Radiology and Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA (Z. Yu, Yu.Zhanyang@mgh.harvard.edu ; Y. Jiang, YJIANG6@mgh.harvare.edu ; I. Chin, icgitar@gmail.com ; E. Lo, lo@helix.mgh.harvard.edu ; X. Wang, wangxi@helix.mgh.harvard.edu ) – name: 2 School of Pharmaceutical Sciences, Key Laboratory of Biotechnology and Pharmaceutical Engineering, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China (L. Lin, linliwz@hotmail.com ; X. Wang, wangxiaojie1972@hotmail.com ; X. Li, xiaokunli@163.net )
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Cites_doi	10.1016/S2213-8587(18)30037-8 10.1371/journal.pone.0122358 10.1523/JNEUROSCI.1683-07.2007 10.1089/ars.2010.3283 10.1007/s12035-017-0544-0 10.1038/onc.2012.493 10.1210/en.2009-0532 10.2337/dc08-2300 10.1016/j.freeradbiomed.2016.02.002 10.3389/fendo.2015.00168 10.1172/JCI23606 10.1016/j.abb.2008.11.016 10.1016/S0006-8993(00)01942-9 10.3389/fchem.2015.00004 10.1172/JCI25102 10.1038/s41419-018-0307-5 10.1080/21688370.2016.1154641 10.4172/2329-6887.1000125 10.3233/JAD-122254 10.1007/978-1-4939-3661-8_10 10.3389/fnins.2017.00224 10.3109/01677063.2015.1067203 10.1523/JNEUROSCI.1304-15.2015 10.1007/s11481-017-9752-7 10.1002/cam4.788 10.1007/s10439-010-0023-5 10.1007/s12035-017-0663-7 10.7554/eLife.00065 10.1074/jbc.M211558200 10.1111/j.1755-5949.2012.00340.x 10.2337/db05-1435 10.1016/j.neulet.2017.05.059 10.1016/j.jash.2010.12.003 10.1210/en.2012-2276 10.1038/bjc.2013.550 10.1210/en.2006-1168 10.1210/en.2008-0816 10.1161/01.STR.21.4.582 10.1007/s00125-006-0485-z 10.1177/0271678X16642233 10.1128/MCB.00225-13 10.1016/j.molmet.2015.06.008 10.1007/978-1-61779-191-8_25 10.1038/nrd4275 10.1128/MCB.24.24.10941-10953.2004 10.1074/jbc.M113.488866
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Keywords	Hyperglycemia Nrf2 Fibroblast growth factor 21 (FGF21) Blood-brain barrier (BBB) Keap1 Inflammation Diabetes FGFR1
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References	Wellen, Hotamisligil (CR33) 2005; 115 Uruno, Furusawa, Yagishita, Fukutomi, Muramatsu, Negishi, Sugawara, Kensler, Yamamoto (CR44) 2013; 33 Wang, Yuan, Yu, Lin, Jiang, Cao, Zhuang, Whalen, Song, Wang, Li, Lo, Xu, Wang (CR16) 2017; 55 Prasad, Sajja, Naik, Cucullo (CR6) 2014; 2 Liu, Wang, Zhang, Wei, Li (CR32) 2012; 18 Straub, Wolfrum (CR10) 2015; 4 Cheng, Zhang, Guo, Li, Sun, Chen, Zhang, Lu, Tan, Feng, Fu, Liu, Xu, Cai (CR26) 2016; 93 Hawkins, Lundeen, Norwood, Brooks, Egleton (CR7) 2007; 50 Cheng, Siow, Mann (CR20) 2011; 14 Sajja, Prasad, Tang, Kaisar, Cucullo (CR22) 2017; 653 Tu, Zhang, Zhu, Dai, Li, Yang, Zhang, Brann, Wang (CR43) 2015; 35 Kharitonenkov, Shiyanova, Koester, Ford, Micanovic, Galbreath, Sandusky, Hammond, Moyers, Owens, Gromada, Brozinick, Hawkins, Wroblewski, Li, Mehrbod, Jaskunas, Shanafelt (CR13) 2005; 115 Baribault (CR46) 2016; 1438 Saczynski, Siggurdsson, Jonsson, Eiriksdottir, Olafsdottir, Kjartansson, Harris, van Buchem, Gudnason, Launer (CR3) 2009; 32 Sajja, Green, Cucullo (CR23) 2015; 10 Lopez, Niu, Huber, Carter (CR39) 2009; 482 Bocci, Valacchi (CR18) 2015; 3 Chen, Yu, Ji, Ma, Chen, Li, Li, Ding, Kang, Huang, Liang, Lin, Cai (CR37) 2016; 5 Wang, Hu (CR1) 2018; 6 Stranahan, Hao, Dey, Yu, Baban (CR29) 2016; 36 Liu, Chern (CR21) 2015; 29 Yang, Feng, Lin, Yu, Lin, Yan, Lu, Zhang (CR25) 2018; 9 Lee, Calkins, Chan, Kan, Johnson (CR17) 2003; 278 Wente, Efanov, Brenner, Kharitonenkov, Koster, Sandusky, Sewing, Treinies, Zitzer, Gromada (CR14) 2006; 55 Cheng, Chang, Leung (CR40) 2013; 288 Zhao, Moore, Redell, Dash (CR36) 2007; 27 Kaya, Ahishali (CR28) 2011; 763 Zhang, Lo, Cross, Templeton, Hannink (CR24) 2004; 24 Nguyen, Tsunematsu, Yanagisawa, Kudo, Miyauchi, Kamata, Takata (CR35) 2013; 109 Haddad-Tovolli, Dragano, Ramalho, Velloso (CR4) 2017; 11 Badman, Koester, Flier, Kharitonenkov, Maratos-Flier (CR11) 2009; 150 Duelli, Maurer, Staudt, Heiland, Duembgen, Kuschinsky (CR5) 2000; 858 Lin, Wang, Qian, Cao, Xiao, Wang, Li, Yu (CR27) 2017; 55 Arlt, Sebens, Krebs, Geismann, Grossmann, Kruse, Schreiber, Schafer (CR38) 2013; 32 Bogush, Heldt, Persidsky (CR2) 2017; 12 Sakata, Mogi, Iwanami, Tsukuda, Min, Jing, Ohshima, Ito, Horiuchi (CR9) 2011; 5 Zhang, Li (CR45) 2015; 6 Acharya, Levin, Clifford, Han, Tourtellotte, Chamberlain, Pollaro, Coretti, Kosciuk, Nagele, Demarshall, Freeman, Shi, Guan, Macphee, Wilensky, Nagele (CR8) 2013; 35 Zhang, Xie, Berglund, Coate, He, Katafuchi, Xiao, Potthoff, Wei, Wan, Yu, Evans, Kliewer, Mangelsdorf (CR12) 2012; 1 Donath (CR34) 2014; 13 Kharitonenkov, Wroblewski, Koester, Chen, Clutinger, Tigno, Hansen, Shanafelt, Etgen (CR41) 2007; 148 Hatashita, Hoff (CR30) 1990; 21 Stamatovic, Johnson, Keep, Andjelkovic (CR31) 2016; 4 Coskun, Bina, Schneider, Dunbar, Hu, Chen, Moller, Kharitonenkov (CR42) 2008; 149 Li, Simon, Cancel, Shi, Ji, Tarbell, Morrison, Fu (CR47) 2010; 38 Kim, Lee, Cha, Hyun, Kim, Lee, Song, Nam, Han, Han, Han, Kang, Cha (CR15) 2013; 154 Kurochkin, Chernov, Kirpichnikov, Kutyshenko, Bruskov (CR19) 1989; 23 JS Saczynski (1234_CR3) 2009; 32 S Hatashita (1234_CR30) 1990; 21 M Kaya (1234_CR28) 2011; 763 M Bogush (1234_CR2) 2017; 12 AV Kurochkin (1234_CR19) 1989; 23 V Bocci (1234_CR18) 2015; 3 RK Sajja (1234_CR22) 2017; 653 T Coskun (1234_CR42) 2008; 149 DD Wang (1234_CR1) 2018; 6 YJ Liu (1234_CR21) 2015; 29 RK Sajja (1234_CR23) 2015; 10 A Kharitonenkov (1234_CR41) 2007; 148 J Zhang (1234_CR45) 2015; 6 JM Lee (1234_CR17) 2003; 278 H Yang (1234_CR25) 2018; 9 HW Kim (1234_CR15) 2013; 154 A Sakata (1234_CR9) 2011; 5 X Cheng (1234_CR20) 2011; 14 A Kharitonenkov (1234_CR13) 2005; 115 BT Hawkins (1234_CR7) 2007; 50 NK Acharya (1234_CR8) 2013; 35 L Straub (1234_CR10) 2015; 4 D Lopez (1234_CR39) 2009; 482 KE Wellen (1234_CR33) 2005; 115 Y Cheng (1234_CR26) 2016; 93 A Arlt (1234_CR38) 2013; 32 H Baribault (1234_CR46) 2016; 1438 L Lin (1234_CR27) 2017; 55 PT Nguyen (1234_CR35) 2013; 109 R Haddad-Tovolli (1234_CR4) 2017; 11 R Duelli (1234_CR5) 2000; 858 Q Wang (1234_CR16) 2017; 55 J Chen (1234_CR37) 2016; 5 Y Zhang (1234_CR12) 2012; 1 AM Stranahan (1234_CR29) 2016; 36 JC Cheng (1234_CR40) 2013; 288 W Wente (1234_CR14) 2006; 55 SM Stamatovic (1234_CR31) 2016; 4 MY Donath (1234_CR34) 2014; 13 G Li (1234_CR47) 2010; 38 WY Liu (1234_CR32) 2012; 18 MK Badman (1234_CR11) 2009; 150 A Uruno (1234_CR44) 2013; 33 J Tu (1234_CR43) 2015; 35 J Zhao (1234_CR36) 2007; 27 S Prasad (1234_CR6) 2014; 2 DD Zhang (1234_CR24) 2004; 24
References_xml	– volume: 6 start-page: 416 year: 2018 end-page: 426 ident: CR1 article-title: Precision nutrition for prevention and management of type 2 diabetes publication-title: Lancet Diabetes Endocrinol doi: 10.1016/S2213-8587(18)30037-8 – volume: 23 start-page: 135 issue: 1 year: 1989 end-page: 152 ident: CR19 article-title: Complete assignment of signals in 1D and 2D H-NMR spectra of a 17-member oligonucleotide, a model symmetrical analog of lambda operators publication-title: Mol Biol (Mosk) – volume: 10 issue: 3 year: 2015 ident: CR23 article-title: Altered Nrf2 signaling mediates hypoglycemia-induced blood-brain barrier endothelial dysfunction in vitro publication-title: PLoS One doi: 10.1371/journal.pone.0122358 – volume: 27 start-page: 10240 issue: 38 year: 2007 end-page: 10248 ident: CR36 article-title: Enhancing expression of Nrf2-driven genes protects the blood brain barrier after brain injury publication-title: J Neurosci doi: 10.1523/JNEUROSCI.1683-07.2007 – volume: 14 start-page: 469 issue: 3 year: 2011 end-page: 487 ident: CR20 article-title: Impaired redox signaling and antioxidant gene expression in endothelial cells in diabetes: a role for mitochondria and the nuclear factor-E2-related factor 2-Kelch-like ECH-associated protein 1 defense pathway publication-title: Antioxid Redox Signal doi: 10.1089/ars.2010.3283 – volume: 55 start-page: 3131 year: 2017 end-page: 3142 ident: CR27 article-title: bFGF protects against oxygen glucose deprivation/reoxygenation-induced endothelial monolayer permeability via S1PR1-dependent mechanisms publication-title: Mol Neurobiol doi: 10.1007/s12035-017-0544-0 – volume: 32 start-page: 4825 issue: 40 year: 2013 end-page: 4835 ident: CR38 article-title: Inhibition of the Nrf2 transcription factor by the alkaloid trigonelline renders pancreatic cancer cells more susceptible to apoptosis through decreased proteasomal gene expression and proteasome activity publication-title: Oncogene doi: 10.1038/onc.2012.493 – volume: 150 start-page: 4931 issue: 11 year: 2009 end-page: 4940 ident: CR11 article-title: Fibroblast growth factor 21-deficient mice demonstrate impaired adaptation to ketosis publication-title: Endocrinology doi: 10.1210/en.2009-0532 – volume: 32 start-page: 1608 issue: 9 year: 2009 end-page: 1613 ident: CR3 article-title: Glycemic status and brain injury in older individuals: the age gene/environment susceptibility-Reykjavik study publication-title: Diabetes Care doi: 10.2337/dc08-2300 – volume: 93 start-page: 94 year: 2016 end-page: 109 ident: CR26 article-title: Up-regulation of Nrf2 is involved in FGF21-mediated fenofibrate protection against type 1 diabetic nephropathy publication-title: Free Radic Biol Med doi: 10.1016/j.freeradbiomed.2016.02.002 – volume: 6 year: 2015 ident: CR45 article-title: Fibroblast growth factor 21 analogs for treating metabolic disorders publication-title: Front Endocrinol (Lausanne) doi: 10.3389/fendo.2015.00168 – volume: 115 start-page: 1627 issue: 6 year: 2005 end-page: 1635 ident: CR13 article-title: FGF-21 as a novel metabolic regulator publication-title: J Clin Invest doi: 10.1172/JCI23606 – volume: 482 start-page: 77 issue: 1–2 year: 2009 end-page: 82 ident: CR39 article-title: Tumor-induced upregulation of twist, snail, and slug represses the activity of the human VE-cadherin promoter publication-title: Arch Biochem Biophys doi: 10.1016/j.abb.2008.11.016 – volume: 858 start-page: 338 issue: 2 year: 2000 end-page: 347 ident: CR5 article-title: Increased cerebral glucose utilization and decreased glucose transporter Glut1 during chronic hyperglycemia in rat brain publication-title: Brain Res doi: 10.1016/S0006-8993(00)01942-9 – volume: 3 year: 2015 ident: CR18 article-title: Nrf2 activation as target to implement therapeutic treatments publication-title: Front Chem doi: 10.3389/fchem.2015.00004 – volume: 115 start-page: 1111 issue: 5 year: 2005 end-page: 1119 ident: CR33 article-title: Inflammation, stress, and diabetes publication-title: J Clin Invest doi: 10.1172/JCI25102 – volume: 9 start-page: 227 issue: 2 year: 2018 ident: CR25 article-title: Fibroblast growth factor-21 prevents diabetic cardiomyopathy via AMPK-mediated antioxidation and lipid-lowering effects in the heart publication-title: Cell Death Dis doi: 10.1038/s41419-018-0307-5 – volume: 4 issue: 1 year: 2016 ident: CR31 article-title: Junctional proteins of the blood-brain barrier: new insights into function and dysfunction publication-title: Tissue Barriers doi: 10.1080/21688370.2016.1154641 – volume: 2 start-page: 125 issue: 2 year: 2014 ident: CR6 article-title: Diabetes mellitus and blood-brain barrier dysfunction: an overview publication-title: Aust J Pharm doi: 10.4172/2329-6887.1000125 – volume: 35 start-page: 179 issue: 1 year: 2013 end-page: 198 ident: CR8 article-title: Diabetes and hypercholesterolemia increase blood-brain barrier permeability and brain amyloid deposition: beneficial effects of the LpPLA2 inhibitor darapladib publication-title: J Alzheimers Dis doi: 10.3233/JAD-122254 – volume: 1438 start-page: 153 year: 2016 end-page: 175 ident: CR46 article-title: Mouse models of type 2 diabetes mellitus in drug discovery publication-title: Methods Mol Biol doi: 10.1007/978-1-4939-3661-8_10 – volume: 11 year: 2017 ident: CR4 article-title: Development and function of the blood-brain barrier in the context of metabolic control publication-title: Front Neurosci doi: 10.3389/fnins.2017.00224 – volume: 29 start-page: 50 issue: 2–3 year: 2015 end-page: 58 ident: CR21 article-title: AMPK-mediated regulation of neuronal metabolism and function in brain diseases publication-title: J Neurogenet doi: 10.3109/01677063.2015.1067203 – volume: 35 start-page: 14727 issue: 44 year: 2015 end-page: 14739 ident: CR43 article-title: Cell-permeable peptide targeting the Nrf2-Keap1 interaction: a potential novel therapy for global cerebral ischemia publication-title: J Neurosci doi: 10.1523/JNEUROSCI.1304-15.2015 – volume: 12 start-page: 593 year: 2017 end-page: 601 ident: CR2 article-title: Blood brain barrier injury in diabetes: unrecognized effects on brain and cognition publication-title: J NeuroImmune Pharmacol doi: 10.1007/s11481-017-9752-7 – volume: 5 start-page: 2678 issue: 10 year: 2016 end-page: 2687 ident: CR37 article-title: Clinical implication of Keap1 and phosphorylated Nrf2 expression in hepatocellular carcinoma publication-title: Cancer Med doi: 10.1002/cam4.788 – volume: 38 start-page: 2499 issue: 8 year: 2010 end-page: 2511 ident: CR47 article-title: Permeability of endothelial and astrocyte cocultures: in vitro blood-brain barrier models for drug delivery studies publication-title: Ann Biomed Eng doi: 10.1007/s10439-010-0023-5 – volume: 55 start-page: 4702 year: 2017 end-page: 4717 ident: CR16 article-title: FGF21 attenuates high-fat diet-induced cognitive impairment via metabolic regulation and anti-inflammation of obese mice publication-title: Mol Neurobiol doi: 10.1007/s12035-017-0663-7 – volume: 1 start-page: e00065 year: 2012 ident: CR12 article-title: The starvation hormone, fibroblast growth factor-21, extends lifespan in mice publication-title: Elife doi: 10.7554/eLife.00065 – volume: 278 start-page: 12029 issue: 14 year: 2003 end-page: 12038 ident: CR17 article-title: Identification of the NF-E2-related factor-2-dependent genes conferring protection against oxidative stress in primary cortical astrocytes using oligonucleotide microarray analysis publication-title: J Biol Chem doi: 10.1074/jbc.M211558200 – volume: 18 start-page: 609 issue: 8 year: 2012 end-page: 615 ident: CR32 article-title: Tight junction in blood-brain barrier: an overview of structure, regulation, and regulator substances publication-title: CNS Neurosci Ther doi: 10.1111/j.1755-5949.2012.00340.x – volume: 55 start-page: 2470 issue: 9 year: 2006 end-page: 2478 ident: CR14 article-title: Fibroblast growth factor-21 improves pancreatic beta-cell function and survival by activation of extracellular signal-regulated kinase 1/2 and Akt signaling pathways publication-title: Diabetes doi: 10.2337/db05-1435 – volume: 653 start-page: 152 year: 2017 end-page: 158 ident: CR22 article-title: Blood-brain barrier disruption in diabetic mice is linked to Nrf2 signaling deficits: role of ABCB10? publication-title: Neurosci Lett doi: 10.1016/j.neulet.2017.05.059 – volume: 5 start-page: 7 issue: 1 year: 2011 end-page: 11 ident: CR9 article-title: Female type 2 diabetes mellitus mice exhibit severe ischemic brain damage publication-title: J Am Soc Hypertens doi: 10.1016/j.jash.2010.12.003 – volume: 154 start-page: 3366 issue: 9 year: 2013 end-page: 3376 ident: CR15 article-title: Fibroblast growth factor 21 improves insulin resistance and ameliorates renal injury in db/db mice publication-title: Endocrinology doi: 10.1210/en.2012-2276 – volume: 109 start-page: 2248 issue: 8 year: 2013 end-page: 2258 ident: CR35 article-title: The FGFR1 inhibitor PD173074 induces mesenchymal-epithelial transition through the transcription factor AP-1 publication-title: Br J Cancer doi: 10.1038/bjc.2013.550 – volume: 148 start-page: 774 issue: 2 year: 2007 end-page: 781 ident: CR41 article-title: The metabolic state of diabetic monkeys is regulated by fibroblast growth factor-21 publication-title: Endocrinology doi: 10.1210/en.2006-1168 – volume: 149 start-page: 6018 issue: 12 year: 2008 end-page: 6027 ident: CR42 article-title: Fibroblast growth factor 21 corrects obesity in mice publication-title: Endocrinology doi: 10.1210/en.2008-0816 – volume: 21 start-page: 582 issue: 4 year: 1990 end-page: 588 ident: CR30 article-title: Brain edema and cerebrovascular permeability during cerebral ischemia in rats publication-title: Stroke doi: 10.1161/01.STR.21.4.582 – volume: 50 start-page: 202 issue: 1 year: 2007 end-page: 211 ident: CR7 article-title: Increased blood-brain barrier permeability and altered tight junctions in experimental diabetes in the rat: contribution of hyperglycaemia and matrix metalloproteinases publication-title: Diabetologia doi: 10.1007/s00125-006-0485-z – volume: 36 start-page: 2108 issue: 12 year: 2016 end-page: 2121 ident: CR29 article-title: Blood-brain barrier breakdown promotes macrophage infiltration and cognitive impairment in leptin receptor-deficient mice publication-title: J Cereb Blood Flow Metab doi: 10.1177/0271678X16642233 – volume: 33 start-page: 2996 issue: 15 year: 2013 end-page: 3010 ident: CR44 article-title: The Keap1-Nrf2 system prevents onset of diabetes mellitus publication-title: Mol Cell Biol doi: 10.1128/MCB.00225-13 – volume: 4 start-page: 605 issue: 9 year: 2015 end-page: 609 ident: CR10 article-title: FGF21, energy expenditure and weight loss - how much brown fat do you need? publication-title: Mol Metab doi: 10.1016/j.molmet.2015.06.008 – volume: 763 start-page: 369 year: 2011 end-page: 382 ident: CR28 article-title: Assessment of permeability in barrier type of endothelium in brain using tracers: Evans blue, sodium fluorescein and horseradish peroxidase publication-title: Methods Mol Biol doi: 10.1007/978-1-61779-191-8_25 – volume: 13 start-page: 465 issue: 6 year: 2014 end-page: 476 ident: CR34 article-title: Targeting inflammation in the treatment of type 2 diabetes: time to start publication-title: Nat Rev Drug Discov doi: 10.1038/nrd4275 – volume: 24 start-page: 10941 issue: 24 year: 2004 end-page: 10953 ident: CR24 article-title: Keap1 is a redox-regulated substrate adaptor protein for a Cul3-dependent ubiquitin ligase complex publication-title: Mol Cell Biol doi: 10.1128/MCB.24.24.10941-10953.2004 – volume: 288 start-page: 33181 issue: 46 year: 2013 end-page: 33192 ident: CR40 article-title: Transforming growth factor-beta1 inhibits trophoblast cell invasion by inducing Snail-mediated down-regulation of vascular endothelial-cadherin protein publication-title: J Biol Chem doi: 10.1074/jbc.M113.488866 – volume: 278 start-page: 12029 issue: 14 year: 2003 ident: 1234_CR17 publication-title: J Biol Chem doi: 10.1074/jbc.M211558200 – volume: 55 start-page: 3131 year: 2017 ident: 1234_CR27 publication-title: Mol Neurobiol doi: 10.1007/s12035-017-0544-0 – volume: 55 start-page: 4702 year: 2017 ident: 1234_CR16 publication-title: Mol Neurobiol doi: 10.1007/s12035-017-0663-7 – volume: 93 start-page: 94 year: 2016 ident: 1234_CR26 publication-title: Free Radic Biol Med doi: 10.1016/j.freeradbiomed.2016.02.002 – volume: 24 start-page: 10941 issue: 24 year: 2004 ident: 1234_CR24 publication-title: Mol Cell Biol doi: 10.1128/MCB.24.24.10941-10953.2004 – volume: 5 start-page: 2678 issue: 10 year: 2016 ident: 1234_CR37 publication-title: Cancer Med doi: 10.1002/cam4.788 – volume: 115 start-page: 1111 issue: 5 year: 2005 ident: 1234_CR33 publication-title: J Clin Invest doi: 10.1172/JCI25102 – volume: 288 start-page: 33181 issue: 46 year: 2013 ident: 1234_CR40 publication-title: J Biol Chem doi: 10.1074/jbc.M113.488866 – volume: 18 start-page: 609 issue: 8 year: 2012 ident: 1234_CR32 publication-title: CNS Neurosci Ther doi: 10.1111/j.1755-5949.2012.00340.x – volume: 32 start-page: 1608 issue: 9 year: 2009 ident: 1234_CR3 publication-title: Diabetes Care doi: 10.2337/dc08-2300 – volume: 858 start-page: 338 issue: 2 year: 2000 ident: 1234_CR5 publication-title: Brain Res doi: 10.1016/S0006-8993(00)01942-9 – volume: 35 start-page: 179 issue: 1 year: 2013 ident: 1234_CR8 publication-title: J Alzheimers Dis doi: 10.3233/JAD-122254 – volume: 23 start-page: 135 issue: 1 year: 1989 ident: 1234_CR19 publication-title: Mol Biol (Mosk) – volume: 13 start-page: 465 issue: 6 year: 2014 ident: 1234_CR34 publication-title: Nat Rev Drug Discov doi: 10.1038/nrd4275 – volume: 32 start-page: 4825 issue: 40 year: 2013 ident: 1234_CR38 publication-title: Oncogene doi: 10.1038/onc.2012.493 – volume: 653 start-page: 152 year: 2017 ident: 1234_CR22 publication-title: Neurosci Lett doi: 10.1016/j.neulet.2017.05.059 – volume: 9 start-page: 227 issue: 2 year: 2018 ident: 1234_CR25 publication-title: Cell Death Dis doi: 10.1038/s41419-018-0307-5 – volume: 21 start-page: 582 issue: 4 year: 1990 ident: 1234_CR30 publication-title: Stroke doi: 10.1161/01.STR.21.4.582 – volume: 6 year: 2015 ident: 1234_CR45 publication-title: Front Endocrinol (Lausanne) doi: 10.3389/fendo.2015.00168 – volume: 2 start-page: 125 issue: 2 year: 2014 ident: 1234_CR6 publication-title: Aust J Pharm doi: 10.4172/2329-6887.1000125 – volume: 27 start-page: 10240 issue: 38 year: 2007 ident: 1234_CR36 publication-title: J Neurosci doi: 10.1523/JNEUROSCI.1683-07.2007 – volume: 38 start-page: 2499 issue: 8 year: 2010 ident: 1234_CR47 publication-title: Ann Biomed Eng doi: 10.1007/s10439-010-0023-5 – volume: 50 start-page: 202 issue: 1 year: 2007 ident: 1234_CR7 publication-title: Diabetologia doi: 10.1007/s00125-006-0485-z – volume: 115 start-page: 1627 issue: 6 year: 2005 ident: 1234_CR13 publication-title: J Clin Invest doi: 10.1172/JCI23606 – volume: 29 start-page: 50 issue: 2–3 year: 2015 ident: 1234_CR21 publication-title: J Neurogenet doi: 10.3109/01677063.2015.1067203 – volume: 11 year: 2017 ident: 1234_CR4 publication-title: Front Neurosci doi: 10.3389/fnins.2017.00224 – volume: 6 start-page: 416 year: 2018 ident: 1234_CR1 publication-title: Lancet Diabetes Endocrinol doi: 10.1016/S2213-8587(18)30037-8 – volume: 10 issue: 3 year: 2015 ident: 1234_CR23 publication-title: PLoS One doi: 10.1371/journal.pone.0122358 – volume: 150 start-page: 4931 issue: 11 year: 2009 ident: 1234_CR11 publication-title: Endocrinology doi: 10.1210/en.2009-0532 – volume: 36 start-page: 2108 issue: 12 year: 2016 ident: 1234_CR29 publication-title: J Cereb Blood Flow Metab doi: 10.1177/0271678X16642233 – volume: 33 start-page: 2996 issue: 15 year: 2013 ident: 1234_CR44 publication-title: Mol Cell Biol doi: 10.1128/MCB.00225-13 – volume: 148 start-page: 774 issue: 2 year: 2007 ident: 1234_CR41 publication-title: Endocrinology doi: 10.1210/en.2006-1168 – volume: 55 start-page: 2470 issue: 9 year: 2006 ident: 1234_CR14 publication-title: Diabetes doi: 10.2337/db05-1435 – volume: 35 start-page: 14727 issue: 44 year: 2015 ident: 1234_CR43 publication-title: J Neurosci doi: 10.1523/JNEUROSCI.1304-15.2015 – volume: 1438 start-page: 153 year: 2016 ident: 1234_CR46 publication-title: Methods Mol Biol doi: 10.1007/978-1-4939-3661-8_10 – volume: 1 start-page: e00065 year: 2012 ident: 1234_CR12 publication-title: Elife doi: 10.7554/eLife.00065 – volume: 482 start-page: 77 issue: 1–2 year: 2009 ident: 1234_CR39 publication-title: Arch Biochem Biophys doi: 10.1016/j.abb.2008.11.016 – volume: 4 start-page: 605 issue: 9 year: 2015 ident: 1234_CR10 publication-title: Mol Metab doi: 10.1016/j.molmet.2015.06.008 – volume: 154 start-page: 3366 issue: 9 year: 2013 ident: 1234_CR15 publication-title: Endocrinology doi: 10.1210/en.2012-2276 – volume: 3 year: 2015 ident: 1234_CR18 publication-title: Front Chem doi: 10.3389/fchem.2015.00004 – volume: 4 issue: 1 year: 2016 ident: 1234_CR31 publication-title: Tissue Barriers doi: 10.1080/21688370.2016.1154641 – volume: 14 start-page: 469 issue: 3 year: 2011 ident: 1234_CR20 publication-title: Antioxid Redox Signal doi: 10.1089/ars.2010.3283 – volume: 763 start-page: 369 year: 2011 ident: 1234_CR28 publication-title: Methods Mol Biol doi: 10.1007/978-1-61779-191-8_25 – volume: 12 start-page: 593 year: 2017 ident: 1234_CR2 publication-title: J NeuroImmune Pharmacol doi: 10.1007/s11481-017-9752-7 – volume: 109 start-page: 2248 issue: 8 year: 2013 ident: 1234_CR35 publication-title: Br J Cancer doi: 10.1038/bjc.2013.550 – volume: 5 start-page: 7 issue: 1 year: 2011 ident: 1234_CR9 publication-title: J Am Soc Hypertens doi: 10.1016/j.jash.2010.12.003 – volume: 149 start-page: 6018 issue: 12 year: 2008 ident: 1234_CR42 publication-title: Endocrinology doi: 10.1210/en.2008-0816
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Snippet	Blood-brain barrier (BBB) damage is a characteristic feature of diabetes mellitus pathology and plays significant roles in diabetes-associated neurological... Blood-brain barrier (BBB) damage is a characteristic feature of diabetes mellitus pathology, and plays significant roles in diabetes-associated neurological...
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SubjectTerms	Animals Biomedical and Life Sciences Biomedicine Blood-brain barrier Blood-Brain Barrier - drug effects Blood-Brain Barrier - pathology Brain injury Cell Biology Cell Membrane Permeability - drug effects Cells, Cultured Diabetes Diabetes mellitus Diabetes mellitus (non-insulin dependent) Diabetes Mellitus, Experimental - drug therapy Diabetes Mellitus, Experimental - genetics Diabetes Mellitus, Type 2 - drug therapy Diabetes Mellitus, Type 2 - genetics Drug development Endothelial cells Endothelial Cells - drug effects Endothelial Cells - metabolism Fibroblast growth factor receptor 1 Fibroblast Growth Factors - pharmacology Fibroblast Growth Factors - therapeutic use Glucose metabolism Humans Hyperglycemia Hyperglycemia - pathology Interleukin 1 Interleukin-1beta - metabolism Kelch-Like ECH-Associated Protein 1 - metabolism Lipid metabolism Male Membrane permeability Mice Microvasculature Models, Biological Neurobiology Neurological diseases Neurology Neurosciences NF-E2-Related Factor 2 - genetics NF-E2-Related Factor 2 - metabolism Permeability Protein Binding - drug effects Proteins Recombinant Proteins - pharmacology Recombinant Proteins - therapeutic use Signal Transduction - drug effects Up-regulation Up-Regulation - drug effects
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Title	Recombinant FGF21 Protects Against Blood-Brain Barrier Leakage Through Nrf2 Upregulation in Type 2 Diabetes Mice
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