ArticleCNS neuroscience & therapeutics2021
Variants of WNT7A and GPR124 are associated with hemorrhagic transformation following intravenous thrombolysis in ischemic stroke.
Article in CNS neuroscience & therapeutics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05585255 (Clinical Significance, Mechanism of Action, and New Targeted Drug Research of DKK2 Protein in Cerebral Ischemia-reperfusion Injury), which is not on this map. Cited by 14 papers.
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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.
Clinical Significance, Mechanism of Action, and New Targeted Drug Research of DKK2 Protein in Cerebral Ischemia-reperfusion Injury
Who cites it
14 citing papers in PubMed, 19 citations in OpenAlex.
- Role of the WNT signalling pathway in physiological and pathological blood-brain barrier.Annals of medicine · 2026Review
- Article
- Compromised endothelial Wnt/β-catenin signaling mediates the blood-brain barrier disruption and leads to neuroinflammation in endotoxemia.Journal of neuroinflammation · 2024Article
- Ischemia-reperfusion injury: molecular mechanisms and therapeutic targets.Signal transduction and targeted therapy · 2024Review
- Shaping the brain vasculature in development and disease in the single-cell era.Nature reviews. Neuroscience · 2023Review
- Efficacy and safety of spot heating and ultrasound irradiation on in vitro and in vivo thrombolysis models.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2022Article
- Lithium attenuates blood-brain barrier damage and brain edema following intracerebral hemorrhage via an endothelial Wnt/β-catenin signaling-dependent mechanism in mice.CNS neuroscience & therapeutics · 2022Article
- Endothelial β-Catenin Deficiency Causes Blood-Brain Barrier BreakdownFrontiers in molecular neuroscience · 2022Article
- Activation of Wnt/Beta-Catenin Signaling Pathway as a Promising Therapeutic Candidate for Cerebral Ischemia/Reperfusion Injury.Frontiers in pharmacology · 2022Review
- Zebrafish as a Model for In-Depth Mechanistic Study for Stroke.Translational stroke research · 2021Review
- Review
- Single-Nucleotide Polymorphisms in Oxidative Stress-Related Genes and the Risk of a Stroke in a Polish Population-A Preliminary Study.Brain sciences · 2021Article
- GAS6/Axl Signaling Modulates Blood-Brain Barrier Function Following Intravenous Thrombolysis in Acute Ischemic Stroke.Frontiers in immunology · 2021Article
- Variants of WNT7A and GPR124 are associated with hemorrhagic transformation following intravenous thrombolysis in ischemic stroke.CNS neuroscience & therapeutics · 2021Article
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Authors and funding
14 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimsThe canonical Wnt signaling pathway plays an essential role in blood-brain barrier integrity and intracerebral hemorrhage in preclinical stroke models. Here, we sought to explore the association between canonical Wnt signaling and hemorrhagic transformation (HT) following intravenous thrombolysis (IVT) in acute ischemic stroke (AIS) patients as well as to determine the underlying cellular mechanisms.
methods355 consecutive AIS patients receiving IVT were included. Blood samples were collected on admission, and HT was detected at 24 hours after IVT. 117 single-nucleotide polymorphisms (SNPs) of 28 Wnt signaling genes and exon sequences of 4 core cerebrovascular Wnt signaling components (GPR124, RECK, FZD4, and CTNNB1) were determined using a customized sequencing chip. The impact of identified genetic variants was further studied in HEK 293T cells using cellular and biochemical assays.
resultsDuring the study period, 80 patients experienced HT with 27 parenchymal hematoma (PH). Compared to the non-PH patients, WNT7A SNPs (rs2163910, P = .001, OR 2.727; rs1124480, P = .002, OR 2.404) and GPR124 SNPs (rs61738775, P = .012, OR 4.883; rs146016051, P < .001, OR 7.607; rs75336000, P = .044, OR 2.503) were selectively enriched in the PH patients. Interestingly, a missense variant of GPR124 (rs75336000, c.3587G>A) identified in the PH patients resulted in a single amino acid alteration (p.Cys1196Tyr) in the intracellular domain of GPR124. This variant substantially reduced the activity of WNT7B-induced canonical Wnt signaling by decreasing the ability of GPR124 to recruit cytoplasmic DVL1 to the cellular membrane.
conclusionVariants of WNT7A and GPR124 are associated with increased risk of PH in patients with AIS after intravenous thrombolysis, likely through regulating the activity of canonical Wnt signaling.
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