ArticleActa neuropathologica2015
PDCD10 (CCM3) regulates brain endothelial barrier integrity in cerebral cavernous malformation type 3: role of CCM3-ERK1/2-cortactin cross-talk.
Article in Acta neuropathologica, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
37 citing papers in PubMed, 61 citations in OpenAlex.
- Cerebral cavernous malformations: epidemiology, molecular pathogenesis, diagnosis and therapy.Molecular biomedicine · 2026Review
- Neutrophil serine proteases degrade endothelial cortactin and promote extravasation.The Journal of cell biology · 2026Article
- Integration of artificial intelligence and high-content screening enabled identification of drugs for long-term treatment of cerebral cavernous malformation disease.bioRxiv : the preprint server for biology · 2025Article
- MAPK signaling and angiopoietin-2 contribute to endothelial permeability in capillary malformations.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Persistent Activation of Endothelial Cells is Linked to Thrombosis and Inflammation in Cerebral Cavernous Malformation Disease.bioRxiv : the preprint server for biology · 2025Article
- Profiling Tight Junction Protein Expression in Brain Vascular Malformations.International journal of molecular sciences · 2025Article
- Cerebral Cavernous Malformation: From Genetics to Pharmacotherapy.Brain and behavior · 2025Review
- The Role of lncRNA-miR-26a-mRNA Network in Cancer Progression and Treatment.Biochemical genetics · 2024Review
- Behavioral impairments are linked to neuroinflammation in mice with Cerebral Cavernous Malformation disease.bioRxiv : the preprint server for biology · 2024Article
- Role of Rho-Associated Kinase in the Pathophysiology of Cerebral Cavernous Malformations.Neurology. Genetics · 2024Review
- Extra-axial cavernous malformations of the foramen magnum: illustrative cases.Journal of neurosurgery. Case lessons · 2023Article
- Case report: Thrombolysis in patients with acute ischemic stroke and cerebral cavernous malformation.Frontiers in neurology · 2023Article
- Neuroinflammation Plays a Critical Role in Cerebral Cavernous Malformation Disease.Circulation research · 2022Article
- Perfusion and Permeability MRI Predicts Future Cavernous Angioma Hemorrhage and Growth.Journal of magnetic resonance imaging : JMRI · 2022Article
- Study of BBB Dysregulation in Neuropathogenicity Using Integrative Human Model of Blood-Brain Barrier.Frontiers in cellular neuroscience · 2022Review
- Phosphopantetheinyl transferase ClbA contributes to the virulence of avian pathogenic Escherichia coli in meningitis infection of mice.PloS one · 2022Article
- Perfusion and permeability as diagnostic biomarkers of cavernous angioma with symptomatic hemorrhage.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2021Article
- Bringing CCM into a dish: cell culture models for cerebral cavernous malformations.Medizinische Genetik : Mitteilungsblatt des Berufsverbandes Medizinische Genetik e.V · 2021Article
- Article
- Astrocytes propel neurovascular dysfunction during cerebral cavernous malformation lesion formation.The Journal of clinical investigation · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Impairment of brain endothelial barrier integrity is critical for cerebral cavernous malformation (CCM) lesion development. The current study investigates changes in tight junction (TJ) complex organization when PDCD10 (CCM3) is mutated/depleted in human brain endothelial cells. Analysis of lesions with CCM3 mutation and brain endothelial cells transfected with CCM3 siRNA (CCM3-knockdown) showed little or no increase in TJ transmembrane and scaffolding proteins mRNA expression, but proteins levels were generally decreased. CCM3-knockdown cells had a redistribution of claudin-5 and occludin from the membrane to the cytosol with no alterations in protein turnover but with diminished protein-protein interactions with ZO-1 and ZO-1 interaction with the actin cytoskeleton. The most profound effect of CCM3 mutation/depletion was on an actin-binding protein, cortactin. CCM3 depletion caused cortactin Ser-phosphorylation, dissociation from ZO-1 and actin, redistribution to the cytosol and degradation. This affected cortical actin ring organization, TJ complex stability and consequently barrier integrity, with constant hyperpermeability to inulin. A potential link between CCM3 depletion and altered cortactin was tonic activation of MAP kinase ERK1/2. ERK1/2 inhibition increased cortactin expression and incorporation into the TJ complex and improved barrier integrity. This study highlights the potential role of CCM3 in regulating TJ complex organization and brain endothelial barrier permeability.
Indexed as
Identifiers
What OpenQuestion holds
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.