ArticleThe Journal of clinical investigation2016
Tie1 controls angiopoietin function in vascular remodeling and inflammation.
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 164 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.
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Who cites it
164 citing papers in PubMed, 289 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
- Aberrant stromal tissue factor localisation and mycolactone-driven vascular dysfunction, exacerbated by IL-1β, are linked to fibrin formation in Buruli ulcer lesions.PLoS pathogens · 2022Trial
- Trial
- Tie2 protects the vasculature against thrombus formation in systemic inflammation.The Journal of clinical investigation · 2018Trial
- Sirt1 transgene delivery improves diabetes-impaired wound healing.Bioactive materials · 2026Article
- 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
- Review
- tRNA-derived small RNAs in ocular neovascular diseases: A systematic review.Non-coding RNA research · 2026Review
- Endocardial TIE2 orchestrates cardiac trabeculation via sequestering FOXO1 within the cytoplasm and stimulating versican cleavage.Development (Cambridge, England) · 2026Article
- Multiple organ dysfunction syndrome: molecular mechanisms and therapeutic strategies.Signal transduction and targeted therapy · 2026Review
- AAV-based gene therapies for neovascular AMD.Gene therapy · 2026Review
- Inactive β1-integrin acts as a junctional scaffold for angiopoietin/TIE2/FOXO1 signaling.The Journal of clinical investigation · 2026Article
- SIRPα extracellular domain shed from neutrophils by ADAM10 aggravates sepsis via initiating nitric oxide release from erythrocyte.Journal of advanced research · 2026Article
- Review
- Loss of angiopoietin-2 leads to region-specific brain malformations and blood-brain barrier leakage.JCI insight · 2026Article
- Decoding organ fibrosis: mechanistic insights and emerging therapeutic strategies.Signal transduction and targeted therapy · 2026Review
- TIE2-positive cells in the nucleus pulposus with a purpose: the who, what and why.Journal of biomedical science · 2026Review
- Multi-tissue transcriptome-wide association study identifies 29 risk genes associated with attention-deficit/hyperactivity disorder.medRxiv : the preprint server for health sciences · 2026Article
- Vertebrate-wide transcriptomic screening identifies immune cell-specific expression of the conserved OR-κ gene.Zoological letters · 2026Article
104 more citing papers are in PubMed but not listed here.
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Authors and funding
17 authors at 7 institutions in 4 countries.
Funding
Abstract
The angiopoietin/Tie (ANG/Tie) receptor system controls developmental and tumor angiogenesis, inflammatory vascular remodeling, and vessel leakage. ANG1 is a Tie2 agonist that promotes vascular stabilization in inflammation and sepsis, whereas ANG2 is a context-dependent Tie2 agonist or antagonist. A limited understanding of ANG signaling mechanisms and the orphan receptor Tie1 has hindered development of ANG/Tie-targeted therapeutics. Here, we determined that both ANG1 and ANG2 binding to Tie2 increases Tie1-Tie2 interactions in a β1 integrin-dependent manner and that Tie1 regulates ANG-induced Tie2 trafficking in endothelial cells. Endothelial Tie1 was essential for the agonist activity of ANG1 and autocrine ANG2. Deletion of endothelial Tie1 in mice reduced Tie2 phosphorylation and downstream Akt activation, increased FOXO1 nuclear localization and transcriptional activation, and prevented ANG1- and ANG2-induced capillary-to-venous remodeling. However, in acute endotoxemia, the Tie1 ectodomain that is responsible for interaction with Tie2 was rapidly cleaved, ANG1 agonist activity was decreased, and autocrine ANG2 agonist activity was lost, which led to suppression of Tie2 signaling. Tie1 cleavage also occurred in patients with hantavirus infection. These results support a model in which Tie1 directly interacts with Tie2 to promote ANG-induced vascular responses under noninflammatory conditions, whereas in inflammation, Tie1 cleavage contributes to loss of ANG2 agonist activity and vascular stability.
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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.