ArticleJCI insight2022
Angiogenesis depends upon EPHB4-mediated export of collagen IV from vascular endothelial cells.
Article in JCI insight, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 34 citations in OpenAlex.
- From Genetic Variants to Immune Dysregulation: Multi-Omics Mendelian Randomization Decodes Molecular Networks in Rosacea.Annals of dermatology · 2026Article
- EphB4/EphrinB2 signaling regulates pericyte-like function of DPSCs in angiogenesis via transcriptional factor SRF.Stem cell research & therapy · 2026Article
- Towards precision medicine for brain arteriovenous malformations.The Journal of clinical investigation · 2026Review
- Chinese capillary malformation-arteriovenous malformation: clinical and genetic analysis of eight cases.Frontiers in medicine · 2026Article
- Identification of Ephrin type-B receptor 4 as a critical mediator of tissue fibrosis.JCI insight · 2025Article
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- Article
- Molecular pathogenesis of Alzheimer's disease onset in a mouse model: effects of cannabidiol treatment.Frontiers in neuroscience · 2025Article
- EPHB4-RASA1 Inhibition of PIEZO1 Ras Activation Drives Lymphatic Valvulogenesis.Circulation research · 2024Article
- Liver sinusoidal endothelial cells contribute to portal hypertension through collagen type IV-driven sinusoidal remodeling.JCI insight · 2024Article
- Eph-ephrin signaling couples endothelial cell sorting and arterial specification.Nature communications · 2024Article
- A temporally-restricted pattern of endothelial cell collagen 4 alpha 1 expression during embryonic development determined with a novel knockin Col4a1-P2A-eGFP mouse line.Genesis (New York, N.Y. : 2000) · 2024Article
- Eph receptors and ephrins in cancer progression.Nature reviews. Cancer · 2024Review
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- Distinct mRNA expression profiles and miRNA regulators of the PI3K/AKT/mTOR pathway in breast cancer: insights into tumor progression and therapeutic targets.Frontiers in oncology · 2024Article
- An EPHB4-RASA1 signaling complex inhibits shear stress-induced Ras-MAPK activation in lymphatic endothelial cells to promote the development of lymphatic vessel valves.bioRxiv : the preprint server for biology · 2023Article
- Mutation of key signaling regulators of cerebrovascular development in vein of Galen malformations.Nature communications · 2023Article
- Effective long-term sirolimus treatment in hypoxemia mainly due to intrapulmonary right-to-left shunt in a patient with multiple vascular anomalies.Orphanet journal of rare diseases · 2023Article
- The Therapeutic Effects of EFNB2-Fc in a Cell Model of Kawasaki Disease.Pharmaceuticals (Basel, Switzerland) · 2023Article
- Microglia refine developing retinal astrocytic and vascular networks through the complement C3/C3aR axis.Development (Cambridge, England) · 2023Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 3 countries.
Funding
Abstract
Capillary malformation-arteriovenous malformation (CM-AVM) is a blood vascular anomaly caused by inherited loss-of-function mutations in RASA1 or EPHB4 genes, which encode p120 Ras GTPase-activating protein (p120 RasGAP/RASA1) and Ephrin receptor B4 (EPHB4). However, whether RASA1 and EPHB4 function in the same molecular signaling pathway to regulate the blood vasculature is uncertain. Here, we show that induced endothelial cell-specific (EC-specific) disruption of Ephb4 in mice resulted in accumulation of collagen IV in the EC ER, leading to EC apoptotic death and defective developmental, neonatal, and pathological angiogenesis, as reported previously in induced EC-specific RASA1-deficient mice. Moreover, defects in angiogenic responses in EPHB4-deficient mice could be rescued by drugs that inhibit signaling through the Ras pathway and drugs that promote collagen IV export from the ER. However, EPHB4-mutant mice that expressed a form of EPHB4 that is unable to physically engage RASA1 but retains protein tyrosine kinase activity showed normal angiogenic responses. These findings provide strong evidence that RASA1 and EPHB4 function in the same signaling pathway to protect against the development of CM-AVM independent of physical interaction and have important implications for possible means of treatment of this disease.
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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.