ArticleMolecular neurobiology2019
Recombinant FGF21 Protects Against Blood-Brain Barrier Leakage Through Nrf2 Upregulation in Type 2 Diabetes Mice.
Article in Molecular neurobiology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 61 citations in OpenAlex.
- Diabetic cerebral microvascular disorder: from key pathologies to targeted interventions.Annals of medicine · 2026Review
- The Interaction Between Insulin Resistance and Neuroinflammation in the Brain and Its Impact on Diabetic Encephalopathy.Biology · 2026Review
- Strategies for blood-brain barrier rejuvenation and repair.Nature reviews. Drug discovery · 2026Review
- FGF-FGFR Signaling in Parkinson's Disease: Mechanistic Links to Ferroptosis and Neuroprotection.Brain sciences · 2026Review
- Fibroblast growth factor 21 (FGF21) promoter methylation drives the progression of chronic hepatitis B by mediating oxidative stress and inflammatory immunity.Microbiology spectrum · 2026Article
- NG2-Glia Cause Diabetic Blood-Brain Barrier Disruption by Secreting MMP-9.Diabetes & metabolism journal · 2026Article
- Comorbidity Between Mood Disorders and Chronic Somatic Diseases, With a Focus on Cardiometabolic Disease, and Its Mechanistic Crosstalk.Depression and anxiety · 2026Review
- Chlorogenic Acid Alleviates the Detrimental Effects of Concurrent Hyperglycemia and Chronic Stress on Brain Homeostasis by Modulating Antioxidative Defense in Adult Zebrafish.Antioxidants (Basel, Switzerland) · 2025Article
- Bridging systemic metabolic dysfunction and Alzheimer's disease: the liver interface.Molecular neurodegeneration · 2025Review
- Protective effects of exerkine on cardiovascular system.Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2025Review
- Upregulation of C1QC as a Mediator of Blood-Brain Barrier Damage in Type 2 Diabetes Mellitus.Molecular neurobiology · 2025Article
- Improvements in Exercise for Alzheimer's Disease: Highlighting FGF21-Induced Cerebrovascular Protection.Neurochemical research · 2025Review
- Investigation of Metabolic and Inflammatory Disorder in the Aging FGF21 Knockout Mouse.Inflammation · 2024Article
- FGF21 relieves calcium oxalate-induced cell injury, apoptosis, oxidative damage and ferroptosis of renal tubular epithelial cells through activating Nrf2 signaling pathway.Cytotechnology · 2024Article
- The role of nonmyocardial cells in the development of diabetic cardiomyopathy and the protective effects of FGF21: a current understanding.Cell communication and signaling : CCS · 2024Review
- Blood-brain barrier disruption: a culprit of cognitive decline?Fluids and barriers of the CNS · 2024Review
- Propofol Suppresses LPS-induced BBB Damage by Regulating miR-130a-5p/ZO-1 Axis.Molecular biotechnology · 2024Article
- The role of FGF-21 in promoting diabetic wound healing by modulating high glucose-induced inflammation.Heliyon · 2024Article
- FGF21 attenuates neuroinflammation following subarachnoid hemorrhage through promoting mitophagy and inhibiting the cGAS-STING pathway.Journal of translational medicine · 2024Article
- Nrf2 Signaling Pathway: a Potential Therapeutic Target in Combating Oxidative Stress and Neurotoxicity in Chemotherapy-Induced Cognitive Impairment.Molecular neurobiology · 2024Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.