ArticleScientific reports2017
Up-regulation of NADPH oxidase-mediated redox signaling contributes to the loss of barrier function in KRIT1 deficient endothelium.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 55 citations in OpenAlex.
- Cerebral cavernous malformations: epidemiology, molecular pathogenesis, diagnosis and therapy.Molecular biomedicine · 2026Review
- MicroRNA-21-3p regulation of NADPH oxidase 4 and vascular endothelial growth factor A contributes to hemorrhage in cerebral cavernous malformations.Non-coding RNA research · 2026Article
- Identification of the adhesion GPCR ADGRL4/ELTD1 as a novel potential prognostic biomarker for cerebral cavernous malformation disease.Molecular medicine (Cambridge, Mass.) · 2026Article
- Unveiling a Novel Molecular Interaction and Pro-Metastatic Signaling Cascades Driven by KRIT1.International journal of molecular sciences · 2026Article
- The Role of Immune Infiltration and Oxidative Stress in the Progression of Cerebral Cavernous Malformation.Brain and behavior · 2026Review
- Circulating Blood Prognostic Biomarker Signatures for Hemorrhagic Cerebral Cavernous Malformations (CCMs).International journal of molecular sciences · 2024Article
- Lectin-type oxidized LDL receptor-1 as a potential therapeutic target for cerebral cavernous malformations treatment.Frontiers in neuroscience · 2024Article
- Spatial Mechano-Signaling Regulation of GTPases through Non-Degradative Ubiquitination.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Impaired retinoic acid signaling in cerebral cavernous malformations.Scientific reports · 2023Article
- Plasma metabolites with mechanistic and clinical links to the neurovascular disease cavernous angioma.Communications medicine · 2023Article
- KRIT1: A Traffic Warden at the Busy Crossroads Between Redox Signaling and the Pathogenesis of Cerebral Cavernous Malformation Disease.Antioxidants & redox signaling · 2023Review
- Multidrug-Loaded Lipid Nanoemulsions for the Combinatorial Treatment of Cerebral Cavernous Malformation Disease.Biomedicines · 2023Article
- KRIT1-mediated regulation of neutrophil adhesion and motility.The FEBS journal · 2023Article
- Distant Recurrence of a Cerebral Cavernous Malformation in the Vicinity of a Developmental Venous Anomaly: Case Report of Local Oxy-Inflammatory Events.International journal of molecular sciences · 2022Article
- Heterozygous Loss of KRIT1 in Mice Affects Metabolic Functions of the Liver, Promoting Hepatic Oxidative and Glycative Stress.International journal of molecular sciences · 2022Article
- Next-Generation Sequencing Advances the Genetic Diagnosis of Cerebral Cavernous Malformation (CCM).Antioxidants (Basel, Switzerland) · 2022Article
- Effects of Natural Polyphenols on Oxidative Stress-Mediated Blood-Brain Barrier Dysfunction.Antioxidants (Basel, Switzerland) · 2022Review
- Contribution of protein-protein interactions to the endothelial-barrier-stabilizing function of KRIT1.Journal of cell science · 2022Article
- Is Location Everything? Regulation of the Endothelial CCM Signaling Complex.Frontiers in cardiovascular medicine · 2022Review
- Protein kinase Cα regulates the nucleocytoplasmic shuttling of KRIT1.Journal of cell science · 2021Article
Corrections and comments
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Authors and funding
13 authors at 5 institutions in 2 countries.
Funding
Abstract
The intracellular scaffold KRIT1/CCM1 is an established regulator of vascular barrier function. Loss of KRIT1 leads to decreased microvessel barrier function and to the development of the vascular disorder Cerebral Cavernous Malformation (CCM). However, how loss of KRIT1 causes the subsequent deficit in barrier function remains undefined. Previous studies have shown that loss of KRIT1 increases the production of reactive oxygen species (ROS) and exacerbates vascular permeability triggered by several inflammatory stimuli, but not TNF-α. We now show that endothelial ROS production directly contributes to the loss of barrier function in KRIT1 deficient animals and cells, as targeted antioxidant enzymes reversed the increase in permeability in KRIT1 heterozygous mice as shown by intravital microscopy. Rescue of the redox state restored responsiveness to TNF-α in KRIT1 deficient arterioles, but not venules. In vitro, KRIT1 depletion increased endothelial ROS production via NADPH oxidase signaling, up-regulated Nox4 expression, and promoted NF-κB dependent promoter activity. Recombinant yeast avenanthramide I, an antioxidant and inhibitor of NF-κB signaling, rescued barrier function in KRIT1 deficient cells. However, KRIT1 depletion blunted ROS production in response to TNF-α. Together, our data indicate that ROS signaling is critical for the loss of barrier function following genetic deletion of KRIT1.
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