ArticleBlood2010
Protein S controls hypoxic/ischemic blood-brain barrier disruption through the TAM receptor Tyro3 and sphingosine 1-phosphate receptor.
Article in Blood, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 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
67 citing papers in PubMed, 114 citations in OpenAlex.
- Expression of TAM receptors and their ligands in unexplained recurrent pregnancy loss.Immunologic research · 2026Article
- Protein S: a vitamin K-dependent factor bridging haemostasis, tissue homeostasis and cancer.The Biochemical journal · 2026Review
- Management of patients with protein s deficiency: focus on clinical course and direct oral anticoagulants.Thrombosis journal · 2026Article
- Paracrine signaling mediators of vascular endothelial barrier dysfunction in sepsis: implications for therapeutic targeting.Tissue barriers · 2026Article
- Distinct TYRO3 and PROS1 expression levels contribute to preeclampsia pathogenesis.Histochemistry and cell biology · 2025Article
- The Vitamin K-Dependent Anticoagulant Factor, Protein S, Regulates Vascular Permeability.Current issues in molecular biology · 2024Article
- The role of vitamin K2 in cognitive impairment: linking vascular health to brain health.Frontiers in aging neuroscience · 2024Review
- Specific antagonist of receptor for advanced glycation end‑products attenuates delirium‑like behaviours induced by sevoflurane anaesthesia with surgery in aged mice partially by improving damage to the blood‑brain barrier.Experimental and therapeutic medicine · 2023Article
- Multifaceted Interplay between Hormones, Growth Factors and Hypoxia in the Tumor Microenvironment.Cancers · 2022Review
- 3K3A-Activated Protein C Protects the Blood-Brain Barrier and Neurons From Accelerated Ischemic Injury Caused by Pericyte Deficiency in Mice.Frontiers in neuroscience · 2022Article
- Connexin43 promotes angiogenesis through activating the HIF-1α/VEGF signaling pathway under chronic cerebral hypoperfusion.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2021Article
- Neutrophil extracellular traps promote tPA-induced brain hemorrhage via cGAS in mice with stroke.Blood · 2021Article
- Imaging the construction of capillary networks in the neonatal mouse brain.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Review
- Increased expression of Protein S in eyes with diabetic retinopathy and diabetic macular edema.Scientific reports · 2021Observational
- Hypoxia and the phenomenon of immune exclusion.Journal of translational medicine · 2021Review
- Mer regulates microglial/macrophage M1/M2 polarization and alleviates neuroinflammation following traumatic brain injury.Journal of neuroinflammation · 2021Article
- The Role of Microglial Phagocytosis in Ischemic Stroke.Frontiers in immunology · 2021Review
- Acute effects of human protein S administration after traumatic brain injury in mice.Neural regeneration research · 2020Article
- Mfsd2a and Spns2 are essential for sphingosine-1-phosphate transport in the formation and maintenance of the blood-brain barrier.Science advances · 2020Article
7 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
The anticoagulant factor protein S (PS) has direct cellular activities. Lack of PS in mice causes lethal coagulopathy, ischemic/thrombotic injuries, vascular dysgenesis, and blood-brain barrier (BBB) disruption with intracerebral hemorrhages. Thus, we hypothesized that PS maintains and/or enhances the BBB integrity. Using a BBB model with human brain endothelial cells, we show PS inhibits time- and dose-dependently (half maximal effective concentration [EC(50)] = 27 +/- 3 nM) oxygen/glucose deprivation-induced BBB breakdown, as demonstrated by measurements of the transmonolayer electrical resistance, permeability of endothelial monolayers to dextran (40 kDa), and rearrangement of F-actin toward the cortical cytoskeletal ring. Using Tyro-3, Axl, and Mer (TAM) receptor, tyrosine kinase silencing through RNA interference, specific N-terminus-blocking antibodies, Tyro3 phosphorylation, and Tyro3-, Axl- and Mer-deficient mouse brain endothelial cells, we show that Tyro3 mediates PS vasculoprotection. After Tyro3 ligation, PS activated sphingosine 1-phosphate receptor (S1P(1)), resulting in Rac1-dependent BBB protection. Using 2-photon in vivo imaging, we show that PS blocks postischemic BBB disruption in Tyro3(+/+), Axl(-/-), and Mer(-/-) mice, but not in Tyro3(-/-) mice or Tyro3(+/+) mice receiving low-dose W146, a S1P(1)-specific antagonist. Our findings indicate that PS protects the BBB integrity via Tyro3 and S1P(1), suggesting potentially novel treatments for neurovascular dysfunction resulting from hypoxic/ischemic BBB damage.
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.