ArticleBrain pathology (Zurich, Switzerland)2020
Endothelium-targeted overexpression of Krüppel-like factor 11 protects the blood-brain barrier function after ischemic brain injury.
Article in Brain pathology (Zurich, Switzerland), 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 38 citations in OpenAlex.
- Engineered nanosponges mitigate peripheral stress-induced neuroinflammation and restore cognitive function.bioRxiv : the preprint server for biology · 2026Article
- GPNMB modulates neutrophil extracellular trap formation: therapeutic implications for ischemic stroke.Journal of neuroinflammation · 2026Article
- Zinc finger proteins (ZFPs) in health and disease.Molecular biomedicine · 2026Review
- Oridonin Preserves Retinal Pigmented Epithelial Cell Tight Junctions and Ameliorates Choroidal Neovascularization.Investigative ophthalmology & visual science · 2025Article
- Implications of Krüppel-like factor signaling in neuroinflammation for neurodegenerative diseases.American journal of translational research · 2025Review
- Endothelial Dysfunctions in Blood-Brain Barrier Breakdown in Alzheimer's Disease: From Mechanisms to Potential Therapies.CNS neuroscience & therapeutics · 2024Review
- Endothelial KLF11 is a novel protector against diabetic atherosclerosis.Cardiovascular diabetology · 2024Article
- Krüppel-like factors: potential roles in blood-brain barrier dysfunction and epileptogenesis.Acta pharmacologica Sinica · 2024Review
- [Upregulating KLF11 ameliorates intestinal inflammation in mice with 2, 4, 6-trinitrobenesulfonic acid-induced colitis by inhibiting the JAK2/STAT3 signaling pathway].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2024Article
- Kruppel-like factor 2 contributes to blood-spinal cord barrier integrity and functional recovery from spinal cord injury by augmenting autophagic flux.Theranostics · 2023Article
- Genetic deletion of Krüppel-like factor 11 aggravates traumatic brain injury.Journal of neuroinflammation · 2022Article
- Inflammatory Responses After Ischemic Stroke.Seminars in immunopathology · 2022Review
- Endothelial KLF11 as a Nephroprotectant in AKI.Kidney360 · 2022Article
- Overexpression of Mitochondrial Ferritin Enhances Blood-Brain Barrier Integrity Following Ischemic Stroke in Mice by Maintaining Iron Homeostasis in Endothelial Cells.Antioxidants (Basel, Switzerland) · 2022Article
- KLF11 Protects against Venous Thrombosis via Suppressing Tissue Factor Expression.Thrombosis and haemostasis · 2022Article
- Calcium/Calmodulin-Dependent Protein Kinase II in Cerebrovascular Diseases.Translational stroke research · 2021Review
- Brain Barriers and brain fluids research in 2020 and the fluids and barriers of the CNS thematic series on advances in in vitro modeling of the blood-brain barrier and neurovascular unit.Fluids and barriers of the CNS · 2021Article
- Zinc Finger Proteins in Neuro-Related Diseases Progression.Frontiers in neuroscience · 2021Review
- The Protective Effect of Quercetin on Endothelial Cells Injured by Hypoxia and Reoxygenation.Frontiers in pharmacology · 2021Article
- The Distinct Roles of Transcriptional Factor KLF11 in Normal Cell Growth Regulation and Cancer as a Mediator of TGF-β Signaling Pathway.International journal of molecular sciences · 2020Review
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
Microvascular endothelial cell (EC) injury and the subsequent blood-brain barrier (BBB) breakdown are frequently seen in many neurological disorders, including stroke. We have previously documented that peroxisome proliferator-activated receptor gamma (PPARγ)-mediated cerebral protection during ischemic insults needs Krüppel-like factor 11 (KLF11) as a critical coactivator. However, the role of endothelial KLF11 in cerebrovascular function and stroke outcome is unclear. This study is aimed at investigating the regulatory role of endothelial KLF11 in BBB preservation and neurovascular protection after ischemic stroke. EC-targeted overexpression of KLF11 significantly mitigated BBB leakage in ischemic brains, evidenced by significantly reduced extravasation of BBB tracers and infiltration of peripheral immune cells, and less brain water content. Endothelial cell-selective KLF11 transgenic (EC-KLF11 Tg) mice also exhibited smaller brain infarct and improved neurological function in response to ischemic insults. Furthermore, EC-targeted transgenic overexpression of KLF11 preserved cerebral tight junction (TJ) levels and attenuated the expression of pro-inflammatory factors in mice after ischemic stroke. Mechanistically, we demonstrated that KLF11 directly binds to the promoter of major endothelial TJ proteins including occludin and ZO-1 to promote their activities. Our data indicate that KLF11 functions at the EC level to preserve BBB structural and functional integrity, and therefore, confers brain protection in ischemic stroke. KLF11 may be a novel therapeutic target for the treatment of ischemic stroke and other neurological conditions involving BBB breakdown and neuroinflammation.
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