ArticleOncotarget2015
Activation of an endothelial Notch1-Jagged1 circuit induces VCAM1 expression, an effect amplified by interleukin-1β.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 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
13 citing papers in PubMed, 28 citations in OpenAlex.
- Review
- Astragaloside IV attenuates hypoxia-reoxygenation-induced endothelial senescence and vascular inflammation by modulating the NOTCH1/VCAM-1 axis.Frontiers in aging neuroscience · 2026Article
- Endothelial Notch1 signaling in white adipose tissue promotes cancer cachexia.Nature cancer · 2023Article
- Notch Signaling in the Vasculature: Angiogenesis and Angiocrine Functions.Cold Spring Harbor perspectives in medicine · 2023Review
- Article
- Adding a "Notch" to Cardiovascular Disease Therapeutics: A MicroRNA-Based Approach.Frontiers in cell and developmental biology · 2021Review
- Arecoline N-oxide regulates oral squamous cell carcinoma development through NOTCH1 and FAT1 expressions.Journal of cellular physiology · 2019Article
- The Use of Nutraceuticals to Counteract Atherosclerosis: The Role of the Notch Pathway.Oxidative medicine and cellular longevity · 2019Review
- NLRP3 inflammasome promotes diabetes-induced endothelial inflammation and atherosclerosis.Diabetes, metabolic syndrome and obesity : targets and therapy · 2019Article
- Notch Signaling in Macrophages in the Context of Cancer Immunity.Frontiers in immunology · 2018Review
- Determination of Genes Related to Uveitis by Utilization of the Random Walk with Restart Algorithm on a Protein-Protein Interaction Network.International journal of molecular sciences · 2017Article
- Notch signaling facilitates crossing of endothelial barriers by tumor cells.Molecular & cellular oncology · 2017Article
- Endothelial Cell Activation Is Regulated by Epidermal Growth Factor-like Domain 7 (Egfl7) during Inflammation.The Journal of biological chemistry · 2016Article
Corrections and comments
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Authors and funding
16 authors at 8 institutions in 4 countries.
Funding
Abstract
The Notch1 and Notch4 signaling pathways regulate endothelial cell homeostasis. Inflammatory cytokines induce the expression of endothelial adhesion molecules, including VCAM1, partly by downregulating Notch4 signaling. We investigated the role of endothelial Notch1 in this IL-1β-mediated process. Brief treatment with IL-1β upregulated endothelial VCAM1 and Notch ligand Jagged1. IL-1β decreased Notch1 mRNA levels, but levels of the active Notch1ICD protein remained constant. IL-1β-mediated VCAM1 induction was downregulated in endothelial cells subjected to pretreatment with a pharmacological inhibitor of the γ-secretase, which activates Notch receptors, producing NotchICD. It was also downregulated in cells in which Notch1 and/or Jagged1 were silenced.Conversely, the forced expression of Notch1ICD in naïve endothelial cells upregulated VCAM1 per se and amplified IL-1β-mediated VCAM1 induction. Jagged1 levels increased and Notch4 signaling was downregulated in parallel. Finally, Notch1ICD and Jagged1 expression was upregulated in the endothelium of the liver in a model of chronic liver inflammation.In conclusion, we describe here a cell-autonomous, pro-inflammatory endothelial Notch1-Jagged1 circuit (i) triggering the expression of VCAM1 even in the absence of inflammatory cytokines and (ii) enhancing the effects of IL-1β. Thus, IL-1β regulates Notch1 and Notch4 activity in opposite directions, consistent with a selective targeting of Notch1 in inflamed endothelium.
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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.