ArticleThe Journal of biological chemistry2011
The matricellular protein cysteine-rich protein 61 (CCN1/Cyr61) enhances physiological adaptation of retinal vessels and reduces pathological neovascularization associated with ischemic retinopathy.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 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
31 citing papers in PubMed, 42 citations in OpenAlex.
- Polyunsaturated Fatty Acid Balance Modulates Microglial State in a Murine Model of Oxygen-Induced Neovascularization.Nutrients · 2026Article
- Polyunsaturated fatty acid balance modulates microglial state in a murine model of oxygen-induced neovascularization.Research square · 2025Article
- CYR61 delivery promotes angiogenesis during bone fracture repair.NPJ Regenerative medicine · 2025Article
- Targeting cell-type-specific, choroid-peripheral immune signaling to treat age-related macular degeneration.Cell reports. Medicine · 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
- CCN1 interacts with integrins to regulate intestinal stem cell proliferation and differentiation.Nature communications · 2022Article
- 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
- CCN1-Yes-Associated Protein Feedback Loop Regulates Physiological and Pathological Angiogenesis.Molecular and cellular biology · 2019Article
- EPStem cells translational medicine · 2019Article
- The matricellular protein CCN1 in tissue injury repair.Journal of cell communication and signaling · 2018Review
- Abscisic acid - an anti-angiogenic phytohormone that modulates the phenotypical plasticity of endothelial cells and macrophages.Journal of cell science · 2018Article
- Enteral Arg-Gln Dipeptide Administration Increases Retinal Docosahexaenoic Acid and Neuroprotectin D1 in a Murine Model of Retinopathy of Prematurity.Investigative ophthalmology & visual science · 2018Article
- The Gene Therapy Resource Program: A Decade of Dedication to Translational Research by the National Heart, Lung, and Blood Institute.Human gene therapy. Clinical development · 2017Article
- A Critical Analysis of the AvailableJournal of ophthalmology · 2017Review
- TGF-β-induced stromal CYR61 promotes resistance to gemcitabine in pancreatic ductal adenocarcinoma through downregulation of the nucleoside transporters hENT1 and hCNT3.Carcinogenesis · 2016Article
- CCN1/Cyr61-PI3K/AKT signaling promotes retinal neovascularization in oxygen-induced retinopathy.International journal of molecular medicine · 2015Article
- Eyeing the Cyr61/CTGF/NOV (CCN) group of genes in development and diseases: highlights of their structural likenesses and functional dissimilarities.Human genomics · 2015Review
- Single and Compound Knock-outs of MicroRNA (miRNA)-155 and Its Angiogenic Gene Target CCN1 in Mice Alter Vascular and Neovascular Growth in the Retina via Resident Microglia.The Journal of biological chemistry · 2015Article
- The matricellular protein CCN1 controls retinal angiogenesis by targeting VEGF, Src homology 2 domain phosphatase-1 and Notch signaling.Development (Cambridge, England) · 2015Article
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 2 countries.
Funding
Abstract
Retinal vascular damages are the cardinal hallmarks of retinopathy of prematurity (ROP), a leading cause of vision impairment and blindness in childhood. Both angiogenesis and vasculogenesis are disrupted in the hyperoxia-induced vaso-obliteration phase, and recapitulated, although aberrantly, in the subsequent ischemia-induced neovessel formation phase of ROP. Yet, whereas the histopathological features of ROP are well characterized, many key modulators with a therapeutic potential remain unknown. The CCN1 protein also known as cysteine-rich protein 61 (Cyr61) is a dynamically expressed, matricellular protein required for proper angiogenesis and vasculogenesis during development. The expression of CCN1 becomes abnormally reduced during the hyperoxic and ischemic phases of ROP modeled in the mouse eye with oxygen-induced retinopathy (OIR). Lentivirus-mediated re-expression of CCN1 enhanced physiological adaptation of the retinal vasculature to hyperoxia and reduced pathological angiogenesis following ischemia. Remarkably, injection into the vitreous of OIR mice of hematopoietic stem cells (HSCs) engineered to express CCN1 harnessed ischemia-induced neovessel outgrowth without adversely affecting the physiological adaptation of retinal vessels to hyperoxia. In vitro exposure of HSCs to recombinant CCN1 induced integrin-dependent cell adhesion, migration, and expression of specific endothelial cell markers as well as many components of the Wnt signaling pathway including Wnt ligands, their receptors, inhibitors, and downstream targets. CCN1-induced Wnt signaling mediated, at least in part, adhesion and endothelial differentiation of cultured HSCs, and inhibition of Wnt signaling interfered with normalization of the retinal vasculature induced by CCN1-primed HSCs in OIR mice. These newly identified functions of CCN1 suggest its possible therapeutic utility in ischemic retinopathy.
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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.