ArticleCirculation research2019
Fine-Tuning of Sox17 and Canonical Wnt Coordinates the Permeability Properties of the Blood-Brain Barrier.
Article in Circulation research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
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Who cites it
58 citing papers in PubMed, 109 citations in OpenAlex.
- Role of the WNT signalling pathway in physiological and pathological blood-brain barrier.Annals of medicine · 2026Review
- Mapping neuro-vascular unit communications reveals distinct angiogenic programs across developing mouse brain regions.Nature communications · 2026Article
- Apolipoprotein D, a Novel Ligand for CD36, Is Essential for Blood-Brain Barrier Integrity.Circulation · 2026Article
- Microglial Fkbp5 Impairs Post-Stroke Vascular Integrity and Regeneration by Promoting Yap1-Mediated Glycolysis and Oxidative Phosphorylation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Development of the blood-brain barrier.Development (Cambridge, England) · 2026Review
- UCH-L1 in Alzheimer's Disease: A Crucial Player in Dementia-Associated Mechanisms.International journal of molecular sciences · 2025Review
- Persistent Activation of Endothelial Cells is Linked to Thrombosis and Inflammation in Cerebral Cavernous Malformation Disease.bioRxiv : the preprint server for biology · 2025Article
- SOX17 in pulmonary arterial hypertension: from development to clinical phenotype.European respiratory review : an official journal of the European Respiratory Society · 2025Review
- Inhibition of neutrophil extracellular traps alleviates blood-brain barrier disruption and cognitive dysfunction via Wnt3/β-catenin/TCF4 signaling in sepsis-associated encephalopathy.Journal of neuroinflammation · 2025Article
- Neuroinflammatory Loop in Schizophrenia, Is There a Relationship with Symptoms or Cognition Decline?International journal of molecular sciences · 2025Review
- Interplay between Netrin-1 and Norrin controls arteriovenous zonation of blood-retina barrier integrity.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Key epigenetic and signaling factors in the formation and maintenance of the blood-brain barrier.eLife · 2024Article
- Compromised endothelial Wnt/β-catenin signaling mediates the blood-brain barrier disruption and leads to neuroinflammation in endotoxemia.Journal of neuroinflammation · 2024Article
- Sox17 protects human brain microvascular endothelial cells from AngII-induced injury by regulating autophagy and apoptosis.Molecular and cellular biochemistry · 2024Article
- Article
- GPR126 is a specifier of blood-brain barrier formation in the mouse central nervous system.The Journal of clinical investigation · 2024Article
- A Neutrophil Hijacking Nanoplatform Reprograming NETosis for Targeted Microglia Polarizing Mediated Ischemic Stroke Treatment.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Article
- Deubiquitinase UCHL1 promotes angiogenesis and blood-spinal cord barrier function recovery after spinal cord injury by stabilizing Sox17.Cellular and molecular life sciences : CMLS · 2024Article
- Transcription factors regulating vasculogenesis and angiogenesis.Developmental dynamics : an official publication of the American Association of Anatomists · 2024Review
Corrections and comments
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Authors and funding
15 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
rationaleThe microvasculature of the central nervous system includes the blood-brain barrier (BBB), which regulates the permeability to nutrients and restricts the passage of toxic agents and inflammatory cells. Canonical Wnt/β-catenin signaling is responsible for the early phases of brain vascularization and BBB differentiation. However, this signal declines after birth, and other signaling pathways able to maintain barrier integrity at postnatal stage are still unknown.
objectiveSox17 (SRY [sex-determining region Y]-box 17) constitutes a major downstream target of Wnt/β-catenin in endothelial cells and regulates arterial differentiation. In the present article, we asked whether Sox17 may act downstream of Wnt/β-catenin in inducing BBB differentiation and maintenance. METHODS AND
resultsUsing reporter mice and nuclear staining of Sox17 and β-catenin, we report that although β-catenin signaling declines after birth, Sox17 activation increases and remains high in the adult. Endothelial-specific inactivation of Sox17 leads to increase of permeability of the brain microcirculation. The severity of this effect depends on the degree of BBB maturation: it is strong in the embryo and progressively declines after birth. In search of Sox17 mechanism of action, RNA sequencing analysis of gene expression of brain endothelial cells has identified members of the Wnt/β-catenin signaling pathway as downstream targets of Sox17. Consistently, we found that Sox17 is a positive inducer of Wnt/β-catenin signaling, and it acts in concert with this pathway to induce and maintain BBB properties. In vivo, inhibition of the β-catenin destruction complex or expression of a degradation-resistant β-catenin mutant, prevent the increase in permeability and retina vascular malformations observed in the absence of Sox17.
conclusionsOur data highlight a novel role for Sox17 in the induction and maintenance of the BBB, and they underline the strict reciprocal tuning of this transcription factor and Wnt/β-catenin pathway. Modulation of Sox17 activity may be relevant to control BBB permeability in pathological conditions.
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