ArticleDevelopment (Cambridge, England)2015
The matricellular protein CCN1 controls retinal angiogenesis by targeting VEGF, Src homology 2 domain phosphatase-1 and Notch signaling.
Article in Development (Cambridge, England), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
What it found
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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.
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Who cites it
38 citing papers in PubMed, 51 citations in OpenAlex.
- Fibulin-1 is required for microvascular integrity in the developing brain and retina.Developmental biology · 2026Article
- Current Evidence on the Potential Role of EndothelialReviews in cardiovascular medicine · 2026Review
- CCN1-induced senescence and dysfunction of umbilical cord blood endothelial colony-forming cells in the pathogenesis of preeclampsia.Frontiers in endocrinology · 2026Article
- Macula densa cell angiogenic mechanisms and their therapeutic potential in kidney disease.Frontiers in bioengineering and biotechnology · 2025Article
- Cellular communication network factor 1 promotes retinal leakage in diabetic retinopathy via inducing neutrophil stasis and neutrophil extracellular traps extrusion.Cell communication and signaling : CCS · 2024Article
- CCN-Hippo YAP signaling in vision and its role in neuronal, glial and vascular cell function and behavior.Journal of cell communication and signaling · 2023Review
- Andrographolide suppresses hypoxia-induced embryonic hyaloid vascular system development through HIF-1a/VEGFR2 signaling pathway.Frontiers in cardiovascular medicine · 2023Article
- Atomic Force Microscopy-Based Measurements of Retinal Microvessel Stiffness in Mice with Endothelial-Specific Deletion of CCN1.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Notch Signaling in the Bone Marrow Lymphopoietic Niche.Frontiers in immunology · 2021Review
- Diabetes Promotes Retinal Vascular Endothelial Cell Injury by Inducing CCN1 Expression.Frontiers in cardiovascular medicine · 2021Article
- Notch in mechanotransduction - from molecular mechanosensitivity to tissue mechanostasis.Journal of cell science · 2020Review
- A CTGF-YAP Regulatory Pathway Is Essential for Angiogenesis and Barriergenesis in the Retina.iScience · 2020Article
- Eyeing the Extracellular Matrix in Vascular Development and Microvascular Diseases and Bridging the Divide between Vascular Mechanics and Function.International journal of molecular sciences · 2020Review
- Article
- Caught between a "Rho" and a hard place: are CCN1/CYR61 and CCN2/CTGF the arbiters of microvascular stiffness?Journal of cell communication and signaling · 2020Review
- Endothelial YAP/TAZ Signaling in Angiogenesis and Tumor Vasculature.Frontiers in oncology · 2020Review
- A Practical Guide to the Automated Analysis of Vascular Growth, Maturation and Injury in the Brain.Frontiers in neuroscience · 2020Article
- CCN1-Yes-Associated Protein Feedback Loop Regulates Physiological and Pathological Angiogenesis.Molecular and cellular biology · 2019Article
- The endothelial tip-stalk cell selection and shuffling during angiogenesis.Journal of cell communication and signaling · 2019Review
- Article
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 1 country.
Funding
Abstract
Physiological angiogenesis depends on the highly coordinated actions of multiple angiogenic regulators. CCN1 is a secreted cysteine-rich and integrin-binding matricellular protein required for proper cardiovascular development. However, our understanding of the cellular origins and activities of this molecule is incomplete. Here, we show that CCN1 is predominantly expressed in angiogenic endothelial cells (ECs) at the leading front of actively growing vessels in the mouse retina. Endothelial deletion of CCN1 in mice using a Cre-Lox system is associated with EC hyperplasia, loss of pericyte coverage and formation of dense retinal vascular networks lacking the normal hierarchical arrangement of arterioles, capillaries and venules. CCN1 is a product of an immediate-early gene that is transcriptionally induced in ECs in response to stimulation by vascular endothelial growth factor (VEGF). We found that CCN1 activity is integrated with VEGF receptor 2 (VEGF-R2) activation and downstream signaling pathways required for tubular network formation. CCN1-integrin binding increased the expression of and association between Src homology 2 domain-containing protein tyrosine phosphatase-1 (SHP-1) and VEGF-R2, which leads to rapid dephosphorylation of VEGF-R2 tyrosine, thus preventing EC hyperproliferation. Predictably, CCN1 further brings receptors/signaling molecules into proximity that are otherwise spatially separated. Furthermore, CCN1 induces integrin-dependent Notch activation in cultured ECs, and its targeted gene inactivation in vivo alters Notch-dependent vascular specification and remodeling, suggesting that functional levels of Notch signaling requires CCN1 activity. These data highlight novel functions of CCN1 as a naturally optimized molecule, fine-controlling key processes in physiological angiogenesis and safeguarding against aberrant angiogenic responses.
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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.