ArticleDisease models & mechanisms2021
Suppressing STAT3 activity protects the endothelial barrier from VEGF-mediated vascular permeability.
Article in Disease models & mechanisms, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 3 of them syntheses that pooled it.
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
42 citing papers in PubMed, 3 syntheses or guidelines pooled it, 70 citations in OpenAlex.
- Exploring the Impact of Extracorporeal Membrane Oxygenation on the Endothelium: A Systematic Review.International journal of molecular sciences · 2024Pooled it
- Prognostic role of elevated VEGF in sepsis: A systematic review and meta-analysis.Frontiers in physiology · 2022Pooled it
- Effects of Flavonoid Supplementation on Nanomaterial-Induced Toxicity: A Meta-Analysis of Preclinical Animal Studies.Frontiers in nutrition · 2022Pooled it
- The Dual Role of VEGF in Intracerebral Haemorrhage: From Pathological Mechanisms to Therapeutic Opportunities.Revista de neurologia · 2026Review
- Lesion size reduction in mouse model of endometriosis following clove (International journal of reproductive biomedicine · 2026Article
- Role of the STAT3 Signaling Pathway in Cell Proliferation and Inflammation in Psoriasis and Approaches for Targeted Therapies: A Review.Medical science monitor : international medical journal of experimental and clinical research · 2026Review
- Article
- Curcumin ameliorates ulcerative colitis via inhibiting STAT3-mediated angiogenesis.Archives of medical science : AMS · 2026Article
- Indole-3-lactic acid protects the gut vascular barrier following intestinal ischemia injury through AhR/Nrf2/STAT3 mediated claudin 2 downregulation.Cell communication and signaling : CCS · 2025Article
- M2 macrophages activate the IL-10/JAK2/STAT3 pathway to induce pathological microangiogenesis in the nucleus pulposus exacerbating intervertebral disc degeneration.Journal of orthopaedic surgery and research · 2025Article
- The role of the tumour microenvironment in lung cancer and its therapeutic implications.Medical oncology (Northwood, London, England) · 2025Review
- Cd248a regulates pericyte development and viability in zebrafish.Communications biology · 2025Article
- The significance of calcium ions in cerebral ischemia-reperfusion injury: mechanisms and intervention strategies.Frontiers in molecular biosciences · 2025Review
- Decoding interaction between mitochondria and endoplasmic reticulum in ischemic myocardial injury: targeting natural medicines.Frontiers in pharmacology · 2025Review
- RECK as a Potential Crucial Molecule for the Targeted Treatment of Sepsis.Journal of inflammation research · 2025Review
- Integrated Local and Systemic Communication Factors Regulate Nascent Hematopoietic Progenitor Escape During Developmental Hematopoiesis.International journal of molecular sciences · 2024Article
- Prolonged Extracorporeal Circulation Leads to Inflammation and Higher Expression of Mediators of Vascular Permeability Through Activation of STAT3 Signaling Pathway in Macrophages.International journal of molecular sciences · 2024Article
- Vascular involvement in idiopathic pulmonary fibrosis.ERJ open research · 2024Review
- Flavonoids with Anti-Angiogenesis Function in Cancer.Molecules (Basel, Switzerland) · 2024Review
- Ubiquitin ligase MDM2 mediates endothelial inflammation in Kawasaki disease vasculitis development.Translational pediatrics · 2024Article
Corrections and comments
- Update of
Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Vascular permeability triggered by inflammation or ischemia promotes edema, exacerbates disease progression and impairs tissue recovery. Vascular endothelial growth factor (VEGF) is a potent inducer of vascular permeability. VEGF plays an integral role in regulating vascular barrier function physiologically and in pathologies, including cancer, stroke, cardiovascular disease, retinal conditions and COVID-19-associated pulmonary edema, sepsis and acute lung injury. Understanding temporal molecular regulation of VEGF-induced vascular permeability will facilitate developing therapeutics to inhibit vascular permeability, while preserving tissue-restorative angiogenesis. Here, we demonstrate that VEGF signals through signal transducer and activator of transcription 3 (STAT3) to promote vascular permeability. We show that genetic STAT3 ablation reduces vascular permeability in STAT3-deficient endothelium of mice and VEGF-inducible zebrafish crossed with CRISPR/Cas9-generated Stat3 knockout zebrafish. Intercellular adhesion molecule 1 (ICAM-1) expression is transcriptionally regulated by STAT3, and VEGF-dependent STAT3 activation is regulated by JAK2. Pyrimethamine, an FDA-approved antimicrobial agent that inhibits STAT3-dependent transcription, substantially reduces VEGF-induced vascular permeability in zebrafish, mouse and human endothelium. Collectively, our findings suggest that VEGF/VEGFR-2/JAK2/STAT3 signaling regulates vascular barrier integrity, and inhibition of STAT3-dependent activity reduces VEGF-induced vascular permeability. This article has an associated First Person interview with the first author of the paper.
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.