ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2018
Connexin 43 gap junctions contribute to brain endothelial barrier hyperpermeability in familial cerebral cavernous malformations type III by modulating tight junction structure.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 65 citations in OpenAlex.
- Latent HIV Infection of BBB Pericytes Enhances Gap Junction-mediated Crosstalk with Endothelial Cells.Molecular neurobiology · 2026Article
- Cerebral cavernous malformations: epidemiology, molecular pathogenesis, diagnosis and therapy.Molecular biomedicine · 2026Review
- Targeting epigenetic remodeling of the blood-brain barrier: current knowledge for drug therapy.Epigenomics · 2026Review
- Dose- and Time-Dependent Modulation of Cx43 and Cx45 Expression and Gap Junction Conductance by Resveratrol.Antioxidants (Basel, Switzerland) · 2026Article
- Temporal Evolution of Brain Inflammation in the Bilateral Common Carotid Artery Stenosis Model of Chronic Cerebral Hypoperfusion.Journal of inflammation research · 2026Review
- Deceiving the gatekeepers: virus modulation of gap junctions.Microbiology and molecular biology reviews : MMBR · 2025Review
- 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
- High-throughput differentiation of human blood vessel organoids reveals overlapping and distinct functions of the cerebral cavernous malformation proteins.Angiogenesis · 2025Article
- Effect of chronic heat stress on duodenal epithelial barrier integrity in low- and high-water-efficient broiler chickens.Frontiers in physiology · 2025Article
- Astrocytic connexin 43-hemichannels aggravate seizures by modulating blood-brain barrier permeability in temporal lobe epilepsy mice.Pediatric discovery · 2024Article
- Pathophysiology in Brain Arteriovenous Malformations: Focus on Endothelial Dysfunctions and Endothelial-to-Mesenchymal Transition.Biomedicines · 2024Review
- O-GlcNAcylation Inhibition Upregulates Connexin43 Expression in the Endothelium to Protect the Tight Junction Barrier in Diabetic Retinopathy.Investigative ophthalmology & visual science · 2023Article
- Trans-Compartmental Regulation of Tight Junction Barrier Function.Tissue barriers · 2023Review
- Connexin 43: An Interface Connecting Neuroinflammation to Depression.Molecules (Basel, Switzerland) · 2023Review
- Connexin 43 across the Vasculature: Gap Junctions and Beyond.Journal of vascular research · 2023Review
- Dysregulated Hemostasis and Immunothrombosis in Cerebral Cavernous Malformations.International journal of molecular sciences · 2022Review
- Acute Methylglyoxal-Induced Damage in Blood-Brain Barrier and Hippocampal Tissue.Neurotoxicity research · 2022Article
- Targeting gliovascular connexins prevents inflammatory blood-brain barrier leakage and astrogliosis.JCI insight · 2022Article
- Connexin and Pannexin Large-Pore Channels in Microcirculation and Neurovascular Coupling Function.International journal of molecular sciences · 2022Review
- Article
Corrections and comments
- Retracted
Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Familial cerebral cavernous malformations type III (fCCM3) is a disease of the cerebrovascular system caused by loss-of-function mutations in ccm3 that result in dilated capillary beds that are susceptible to hemorrhage. Before hemorrhage, fCCM3 lesions are characterized by a hyperpermeable blood-brain barrier (BBB), the key pathologic feature of fCCM3. We demonstrate that connexin 43 (Cx43), a gap junction (GJ) protein that is incorporated into the BBB junction complex, is up-regulated in lesions of a murine model of fCCM3. Small interfering RNA-mediated ccm3 knockdown (CCM3KD) in brain endothelial cells in vitro increased Cx43 protein expression, GJ plaque size, GJ intracellular communication (GJIC), and barrier permeability. CCM3KD hyperpermeability was rescued by GAP27, a peptide gap junction and hemichannel inhibitor of Cx43 GJIC. Tight junction (TJ) protein, zonula occludens 1 (ZO-1), accumulated at Cx43 GJs in CCM3KD cells and displayed fragmented staining at TJs. The GAP27-mediated inhibition of Cx43 GJs in CCM3KD cells restored ZO-1 to TJ structures and reduced plaque accumulation at Cx43 GJs. The TJ protein, Claudin-5, was also fragmented at TJs in CCM3KD cells, and GAP27 treatment lengthened TJ-associated fragments and increased Claudin 5-Claudin 5 transinteraction. Overall, we demonstrate that Cx43 GJs are aberrantly increased in fCCM3 and regulate barrier permeability by a TJ-dependent mechanism.-Johnson, A. M., Roach, J. P., Hu, A., Stamatovic, S. M., Zochowski, M. R., Keep, R. F., Andjelkovic, A. V. Connexin 43 gap junctions contribute to brain endothelial barrier hyperpermeability in familial cerebral cavernous malformations type III by modulating tight junction structure.
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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.