ArticleScience translational medicine2017
Targeting STUB1-tissue factor axis normalizes hyperthrombotic uremic phenotype without increasing bleeding risk.
Article in Science translational medicine, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 52 citations in OpenAlex.
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- Tryptophan metabolism reprogramming potentially contributes to the prothrombotic milieu in mice and humans with SARS-CoV-2.Blood vessels, thrombosis & hemostasis · 2026Article
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- A guide to uraemic toxicity.Nature reviews. Nephrology · 2026Review
- Dietary tryptophan augments cancer-associated venous thrombogenicity mitigated by indoleamine 2,3-dioxygenase 1 inhibition.Blood advances · 2025Article
- Stub1 Acetylation by CBP/p300 Attenuates Chronic Hypoxic-Driven Pulmonary Hypertension by Suppressing HIF-2α.American journal of respiratory cell and molecular biology · 2025Article
- Activation and targetability of TYMP-IL-6-TF signaling in the skin microenvironment in uremic calciphylaxis.Science translational medicine · 2025Article
- Novel tissue biomarker candidates to predict both deep venous thrombosis and healing outcome after Achilles tendon rupture.Scientific reports · 2025Article
- Decrease in platelet count in patients with AKI and its association with major adverse kidney events.Renal failure · 2024Article
- STUB1 exacerbates calcium oxalate-induced kidney injury by modulating reactive oxygen species-mediated cellular autophagy via regulating CFTR ubiquitination.Urolithiasis · 2024Article
- Review
- Tryptophan Metabolites Target Transmembrane and Immunoglobulin Domain-Containing 1 Signaling to Augment Renal Tubular Injury.The American journal of pathology · 2023Article
- Chronic Kidney Disease Induces Proarrhythmic Remodeling.Circulation. Arrhythmia and electrophysiology · 2023Article
- Tissue Factor, Thrombosis, and Chronic Kidney Disease.Biomedicines · 2022Review
- Pharmacologic Manipulation of Late SV40 Factor Suppresses Wnt Signaling and Inhibits Growth of Allogeneic and Syngeneic Colon Cancer Xenografts.The American journal of pathology · 2022Article
- Vascular endothelial tissue factor contributes to trimethylamine N-oxide-enhanced arterial thrombosis.Cardiovascular research · 2022Article
- Tryptophan metabolites suppress the Wnt pathway and promote adverse limb events in chronic kidney disease.The Journal of clinical investigation · 2022Article
- Comprehensive Analysis of Endoplasmic Reticulum Stress in Intracranial Aneurysm.Frontiers in cellular neuroscience · 2022Article
- Determinants of Hemodialysis Performance: Modeling Fluid and Solute Transport in Hollow-Fiber Dialyzers.Regenerative engineering and translational medicine · 2021Article
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21 authors at 5 institutions in 3 countries.
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Abstract
Chronic kidney disease (CKD/uremia) remains vexing because it increases the risk of atherothrombosis and is also associated with bleeding complications on standard antithrombotic/antiplatelet therapies. Although the associations of indolic uremic solutes and vascular wall proteins [such as tissue factor (TF) and aryl hydrocarbon receptor (AHR)] are being defined, the specific mechanisms that drive the thrombotic and bleeding risks are not fully understood. We now present an indolic solute-specific animal model, which focuses on solute-protein interactions and shows that indolic solutes mediate the hyperthrombotic phenotype across all CKD stages in an AHR- and TF-dependent manner. We further demonstrate that AHR regulates TF through STIP1 homology and U-box-containing protein 1 (STUB1). As a ubiquitin ligase, STUB1 dynamically interacts with and degrades TF through ubiquitination in the uremic milieu. TF regulation by STUB1 is supported in humans by an inverse relationship of STUB1 and TF expression and reduced STUB1-TF interaction in uremic vessels. Genetic or pharmacological manipulation of STUB1 in vascular smooth muscle cells inhibited thrombosis in flow loops. STUB1 perturbations reverted the uremic hyperthrombotic phenotype without prolonging the bleeding time, in contrast to heparin, the standard-of-care antithrombotic in CKD patients. Our work refines the thrombosis axis (STUB1 is a mediator of indolic solute-AHR-TF axis) and expands the understanding of the interconnected relationships driving the fragile thrombotic state in CKD. It also establishes a means of minimizing the uremic hyperthrombotic phenotype without altering the hemostatic balance, a long-sought-after combination in CKD patients.
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