ArticleRedox biology2025
Ref-1 redox activity modulates canonical Wnt signaling in endothelial cells.
Article in Redox biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed.
- The calcium pump ATP2B1/PMCA1 regulates CNS vascular development by facilitating Norrin- and WNT7A/B-induced Frizzled4 signaling.Cell reports · 2026Article
- APE1/Ref-1: multifunctional biology, selective inhibition, and the path to clinical translation.Expert opinion on therapeutic targets · 2026Review
- The genetic association of miR-34a-5p rs72631823 with the susceptibility to obstetric antiphospholipid syndrome.BMC women's health · 2026Article
- EndMT in vascular cognitive impairment and dementia: mechanisms, evidence gaps, and therapeutic opportunities.Molecular medicine (Cambridge, Mass.) · 2026Review
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Authors and funding
13 authors.
Funding
Abstract
Ischemic retinopathies, including proliferative diabetic retinopathy (PDR) and retinopathy of prematurity (ROP), are characterized by abnormal retinal neovascularization and can lead to blindness in children and adults. Current treatments, such as intravitreal anti-VEGF injections, face limitations due to high treatment burden and variable efficacy, as multiple signaling pathways, beyond VEGF, contribute to retinal neovascularization. Previous studies demonstrate that targeting the redox-mediated transcriptional regulatory function of APE1/Ref-1 reduces pathological neovascularization. We aimed to identify novel signaling pathways regulated by Ref-1 redox activity utilizing RNA sequencing of human retinal endothelial cells (HRECs) treated with a Ref-1 redox inhibitor. We found that Wnt/β-catenin signaling was significantly downregulated after Ref-1 inhibition. Given the role of Wnt signaling in vascular pathologies, we investigated how Ref-1 regulates Wnt/β-catenin signaling. Ref-1 inhibition downregulated Wnt co-receptors LRP5/6 at both the mRNA and protein levels in endothelial cells, suggesting transcriptional regulation. Ref-1 redox inhibitors APX3330 and APX2009 reduced Wnt3a-induced nuclear β-catenin levels, decreased Wnt transcriptional activity by TOPFlash luciferase assay, and blocked hypoxia-induced Wnt/β-catenin activation in HRECs. In the oxygen-induced retinopathy mouse model of retinal neovascularization, Ref-1 specific inhibitor APX2009 reduced the expression of Wnt-related genes at sites of neovascularization. These findings reveal a novel role for Ref-1 redox activity in modulating Wnt/β-catenin signaling in endothelial cells and highlight the potential of Ref-1 redox activity targeted inhibitors as a novel therapeutic approach for retinal neovascular diseases by modulating multiple disease-relevant pathways.
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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.