ArticleScientific reports2018
Expression of periaxin (PRX) specifically in the human cerebrovascular system: PDZ domain-mediated strengthening of endothelial barrier function.
Article in Scientific reports, 2018. 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, 32 citations in OpenAlex.
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- Abnormal Splicing in the Final Intron of PRX Results in Dominant Congenital Cataract Without Neurological Phenotype.Investigative ophthalmology & visual science · 2025Article
- Spatial organization, chromatin accessibility and gene-regulatory programs defining mouse sensory neurons.Communications biology · 2025Article
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- Lung endothelium, tau, and amyloids in health and disease.Physiological reviews · 2024Review
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- Single cell transcriptomic analysis of murine lung development on hyperoxia-induced damage.Nature communications · 2021Article
- A Pulmonary Vascular Model From Endothelialized Whole Organ Scaffolds.Frontiers in bioengineering and biotechnology · 2021Article
- Transcriptomic comparison of human and mouse brain microvessels.Scientific reports · 2020Article
- Modeling blood-brain barrier pathology in cerebrovascular disease in vitro: current and future paradigms.Fluids and barriers of the CNS · 2020Review
- Flexible Players within the Sheaths: The Intrinsically Disordered Proteins of Myelin in Health and Disease.Cells · 2020Review
- Novel mutation in the periaxin gene causal to Charcot-Marie-Tooth disease type 4F.The Journal of international medical research · 2020Article
- Tripartite factors leading to molecular divergence between human and murine smooth muscle.PloS one · 2020Article
- Endothelial Targets in Stroke: Translating Animal Models to Human.Arteriosclerosis, thrombosis, and vascular biology · 2019Review
- The year in review: progress in brain barriers and brain fluid research in 2018.Fluids and barriers of the CNS · 2019Article
- Memory deficits in males and females long after subchronic immune challenge.Neurobiology of learning and memory · 2019Article
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Authors and funding
8 authors at 1 institution in 1 country.
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Abstract
Regulation of cerebral endothelial cell function plays an essential role in changes in blood-brain barrier permeability. Proteins that are important for establishment of endothelial tight junctions have emerged as critical molecules, and PDZ domain containing-molecules are among the most important. We have discovered that the PDZ-domain containing protein periaxin (PRX) is expressed in human cerebral endothelial cells. Surprisingly, PRX protein is not detected in brain endothelium in other mammalian species, suggesting that it could confer human-specific vascular properties. In endothelial cells, PRX is predominantly localized to the nucleus and not tight junctions. Transcriptome analysis shows that PRX expression suppresses, by at least 50%, a panel of inflammatory markers, of which 70% are Type I interferon response genes; only four genes were significantly activated by PRX expression. When expressed in mouse endothelial cells, PRX strengthens barrier function, significantly increases transendothelial electrical resistance (~35%; p < 0.05), and reduces the permeability of a wide range of molecules. The PDZ domain of PRX is necessary and sufficient for its barrier enhancing properties, since a splice variant (S-PRX) that contains only the PDZ domain, also increases barrier function. PRX also attenuates the permeability enhancing effects of lipopolysaccharide. Collectively, these studies suggest that PRX could potentially regulate endothelial homeostasis in human cerebral endothelial cells by modulating inflammatory gene programs.
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