ArticleThe Journal of clinical investigation2016
Opposing actions of angiopoietin-2 on Tie2 signaling and FOXO1 activation.
Article in The Journal of clinical investigation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 160 papers.
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Who cites it
160 citing papers in PubMed, 235 citations in OpenAlex.
- Fluid bolus increases plasma hyaluronan concentration compared to follow-up strategy without a bolus in oliguric intensive care unit patients.Scientific reports · 2024Trial
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- Tie2 protects the vasculature against thrombus formation in systemic inflammation.The Journal of clinical investigation · 2018Trial
- Tie1 ectodomain cleavage governs vascular responses to inflammatory stimulation but is dispensable for angiogenic signaling.The Journal of clinical investigation · 2026Article
- Cellular and signalling mechanisms that regulate the blood-brain barrier.Nature reviews. Molecular cell biology · 2026Review
- Serum Angiopoietin-1 and Angiopoietin-2 as Biomarkers of Pulmonary Hemodynamic Burden in COPD-Associated Pulmonary Hypertension: A Cross-Sectional Study.Advances in respiratory medicine · 2026Article
- Review
- Myovascular Niche: The Role of Endothelial Cells in Skeletal Muscle Health and Disease.Circulation research · 2026Review
- Circulating angiopoietin-2 and TEK receptor tyrosine kinase-2 protein provide prognostic value in patients with acute myocardial infarction.BMC cardiovascular disorders · 2026Article
- Inactive β1-integrin acts as a junctional scaffold for angiopoietin/TIE2/FOXO1 signaling.The Journal of clinical investigation · 2026Article
- Mechanisms of Pericyte-Mediated Cancer Metastasis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Real-world performance of faricimab for neovascular age-related macular degeneration and diabetic macular edema: experience from the BrazilRetNet multicenter study. Report 1.International journal of retina and vitreous · 2026Article
- Single-cell transcriptomic analyses reveal angiogenic vascular responses to chronic cerebral hypoperfusion.iScience · 2026Article
- Loss of angiopoietin-2 leads to region-specific brain malformations and blood-brain barrier leakage.JCI insight · 2026Article
- Urinary angiopoietin-2 is associated with adverse kidney outcomes in the ICU.Critical care (London, England) · 2026Article
- TIE2-positive cells in the nucleus pulposus with a purpose: the who, what and why.Journal of biomedical science · 2026Review
- A Highly Active Angiopoietin 1 Mimetic Potentiates Angiogenesis in Mouse Models of Choroidal Neovascularization.Translational vision science & technology · 2026Article
- The stroke risk gene Foxf2 maintains brain endothelial cell function via Tie2 signaling.Nature neuroscience · 2026Article
- Angiopoietin-2 aggravates Alzheimer's disease by promoting blood-brain barrier dysfunction and neuroinflammation.Cell reports · 2026Article
- Deletion of the angiopoietin receptor Tie2 enhances proliferation and sprouting of cardiac endothelial cells.Angiogenesis · 2026Article
100 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
Abstract
Angiopoietin-2 (ANG2) regulates blood vessel remodeling in many pathological conditions through differential effects on Tie2 signaling. While ANG2 competes with ANG1 to inhibit Tie2, it can paradoxically also promote Tie2 phosphorylation (p-Tie2). A related paradox is that both inactivation and overactivation of Tie2 can result in vascular remodeling. Here, we reconciled these opposing actions of ANG2 by manipulating conditions that govern its actions in the vasculature. ANG2 drove vascular remodeling during Mycoplasma pulmonis infection by acting as a Tie2 antagonist, which led to p-Tie2 suppression, forkhead box O1 (FOXO1) activation, increased ANG2 expression, and vessel leakiness. These changes were exaggerated by anti-Tie2 antibody, inhibition of PI3K signaling, or ANG2 overexpression and were reduced by anti-ANG2 antibody or exogenous ANG1. In contrast, under pathogen-free conditions, ANG2 drove vascular remodeling by acting as an agonist, promoting high p-Tie2, low FOXO1 activation, and no leakage. Tie1 activation was strong under pathogen-free conditions, but infection or TNF-α led to Tie1 inactivation by ectodomain cleavage and promoted the Tie2 antagonist action of ANG2. Together, these data indicate that ANG2 activation of Tie2 supports stable enlargement of normal nonleaky vessels, but reduction of Tie1 in inflammation leads to ANG2 antagonism of Tie2 and initiates a positive feedback loop wherein FOXO1-driven ANG2 expression promotes vascular remodeling and leakage.
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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.