ArticleJCI insight2019
A collagen IV-derived peptide disrupts α5β1 integrin and potentiates Ang2/Tie2 signaling.
Article in JCI insight, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 53 citations in OpenAlex.
- Implantable ocular therapeutic systems: an insight into their clinical potential in the long-term treatment of ocular diseases.Biofabrication · 2026Review
- The Adipokine Hypothesis of Heart Failure With a Preserved Ejection Fraction: A Novel Framework to Explain Pathogenesis and Guide Treatment.Journal of the American College of Cardiology · 2025Review
- Bispecific receptor decoy proteins block ocular neovascularization via simultaneous blockade of vascular endothelial growth factor A and C.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Scutellarin attenuates hypoxia-induced retinal neovascularization through bidirectional modulation of the VEGF/Ang/Tie2 pathway.Frontiers in pharmacology · 2025Article
- Insights to Ang/Tie signaling pathway: another rosy dawn for treating retinal and choroidal vascular diseases.Journal of translational medicine · 2024Review
- Beyond VEGF: Angiopoietin-Tie Signaling Pathway in Diabetic Retinopathy.Journal of clinical medicine · 2024Review
- Protective role of 17β-estradiol in alcohol-associated liver fibrosis is mediated by suppression of integrin signaling.Hepatology communications · 2024Article
- Intrinsic endothelial hyperresponsiveness to inflammatory mediators drives acute episodes in models of Clarkson disease.The Journal of clinical investigation · 2024Article
- Tyrosine Kinase Inhibitors and their role in treating neovascular age-related macular degeneration and diabetic macular oedema.Eye (London, England) · 2023Review
- Gel-forming therapeutic peptide exhibits sustained delivery and efficacy in a mouse model of triple-negative breast cancer.Peptides · 2023Article
- ANG2 Blockade Diminishes Proangiogenic Cerebrovascular Defects Associated With Models of Hereditary Hemorrhagic Telangiectasia.Arteriosclerosis, thrombosis, and vascular biology · 2023Article
- A Triple-Targeted Rutin-Based Self-Assembled Delivery Vector for Treating Ischemic Stroke by Vascular Normalization and Anti-Inflammation via ACE2/Ang1-7 Signaling.ACS central science · 2023Article
- Article
- The Role of Angiopoietins in Neovascular Diabetes-Related Retinal Diseases.Diabetes therapy : research, treatment and education of diabetes and related disorders · 2022Review
- Diabetic Macular Edema: Current Understanding, Molecular Mechanisms and Therapeutic Implications.Cells · 2022Review
- Angiopoietin2-mediated caveolin1 phosphorylation regulating transcytosis of renal tubular epithelial cell contributes to the occurrence of albuminuria under high glucose exposure.Journal of translational medicine · 2022Article
- Screening of Self-Assembling of Collagen IV Fragments into Stable Structures Potentially Useful in Regenerative Medicine.International journal of molecular sciences · 2021Article
- Recent Advancements in the Medical Treatment of Diabetic Retinal Disease.International journal of molecular sciences · 2021Review
- A systems biology model of junctional localization and downstream signaling of the Ang-Tie signaling pathway.NPJ systems biology and applications · 2021Article
- Single-Cell Analysis of Blood-Brain Barrier Response to Pericyte Loss.Circulation research · 2021Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
The angiopoietin (Ang)/Tie2 signaling pathway is essential for maintaining vascular homeostasis, and its dysregulation is associated with several diseases. Interactions between Tie2 and α5β1 integrin have emerged as part of this control; however, the mechanism is incompletely understood. AXT107, a collagen IV-derived peptide, has strong antipermeability activity and has enabled the elucidation of this previously undetermined mechanism. Previously, AXT107 was shown to inhibit VEGFR2 and other growth factor signaling via receptor tyrosine kinase association with specific integrins. AXT107 disrupts α5β1 and stimulates the relocation of Tie2 and α5 to cell junctions. In the presence of Ang2 and AXT107, junctional Tie2 is activated, downstream survival signals are upregulated, F-actin is rearranged to strengthen junctions, and, as a result, endothelial junctional permeability is reduced. These data suggest that α5β1 sequesters Tie2 in nonjunctional locations in endothelial cell membranes and that AXT107-induced disruption of α5β1 promotes clustering of Tie2 at junctions and converts Ang2 into a strong agonist, similar to responses observed when Ang1 levels greatly exceed those of Ang2. The potentiation of Tie2 activation by Ang2 even extended to mouse models in which AXT107 induced Tie2 phosphorylation in a model of hypoxia and inhibited vascular leakage in an Ang2-overexpression transgenic model and an LPS-induced inflammation model. Because Ang2 levels are very high in ischemic diseases, such as diabetic macular edema, neovascular age-related macular degeneration, uveitis, and cancer, targeting α5β1 with AXT107 provides a potentially more effective approach to treat these diseases.
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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.