ArticlePloS one2012
Arhgef15 promotes retinal angiogenesis by mediating VEGF-induced Cdc42 activation and potentiating RhoJ inactivation in endothelial cells.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 1 of them a synthesis that pooled it.
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Who cites it
40 citing papers in PubMed, 1 synthesis or guideline pooled it, 56 citations in OpenAlex.
- The Role of RhoJ in Endothelial Cell Biology and Tumor Pathology.BioMed research international · 2016Pooled it
- Multi-Omics and Functional Analysis ofToxins · 2026Article
- Stromal ARHGEF15 Correlates With Inflammatory EMT and Stromal-Immune Crosstalk During Inflammatory Bowel Disease-To-Colorectal Cancer Progression.Bioinformatics and biology insights · 2026Article
- CDC42-effector interaction inhibitors alter patterns of vessel arborization in skin and tumorsiScience · 2025Article
- The pathogenesis of cerebral small vessel disease and vascular cognitive impairment.Physiological reviews · 2025Review
- SCIG: Machine learning uncovers cell identity genes in single cells by genetic sequence codes.Nucleic acids research · 2025Article
- Activity-dependent regulation of Cdc42 by Ephexin5 drives synapse growth and stabilization.Science advances · 2025Article
- Sinomenine attenuates uremia vascular calcification by miR-143-5p.Scientific reports · 2025Article
- RhoJ: an emerging biomarker and target in cancer research and treatment.Cancer gene therapy · 2024Review
- New Mechanisms Underlying Oncogenesis in Dbl Family Rho Guanine Nucleotide Exchange Factors.Molecular pharmacology · 2024Review
- Ephexin3/ARHGEF5 Together with Cell Migration Signaling Partners within the Tumor Microenvironment Define Prognostic Transcriptional Signatures in Multiple Cancer Types.International journal of molecular sciences · 2023Article
- Whole-Exome Sequencing of 21 Families: Candidate Genes for Early-Onset High Myopia.International journal of molecular sciences · 2023Article
- A gene-based association test of interactions for maternal-fetal genotypes identifies genes associated with nonsyndromic congenital heart defects.Genetic epidemiology · 2023Article
- Mutations in ARHGEF15 cause autosomal dominant hereditary cerebral small vessel disease and osteoporotic fracture.Acta neuropathologica · 2023Article
- Alternative Splicing Changes Promoted by NOVA2 Upregulation in Endothelial Cells and Relevance for Gastric Cancer.International journal of molecular sciences · 2023Article
- PlexinD1 signaling controls domain-specific dendritic development in newborn neurons in the postnatal olfactory bulb.Frontiers in neuroscience · 2023Article
- Actin cytoskeleton in angiogenesis.Biology open · 2022Review
- RNA-Seq Provides Insights into VEGF-Induced Signaling in Human Retinal Microvascular Endothelial Cells: Implications in Retinopathy of Prematurity.International journal of molecular sciences · 2022Article
- Identification of Arhgef12 and Prkci as genetic modifiers of retinal dysplasia in the Crb1rd8 mouse model.PLoS genetics · 2022Article
- A functional antagonism between RhoJ and Cdc42 regulates fibronectin remodelling during angiogenesis.Small GTPases · 2021Article
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundDrugs inhibiting vascular endothelial growth factor (VEGF) signaling are globally administered to suppress deregulated angiogenesis in a variety of eye diseases. However, anti-VEGF therapy potentially affects the normal functions of retinal neurons and glias which constitutively express VEGF receptor 2. Thus, it is desirable to identify novel drug targets which are exclusively expressed in endothelial cells (ECs). Here we attempted to identify an EC-specific Rho guanine nucleotide exchange factor (GEF) and evaluate its role in retinal angiogenesis. METHODOLOGY/PRINCIPAL
findingsBy exploiting fluorescence-activated cell sorting and microarray analyses in conjunction with in silico bioinformatics analyses, we comprehensively identified endothelial genes in angiogenic retinal vessels of postnatal mice. Of 9 RhoGEFs which were highly expressed in retinal ECs, we show that Arhgef15 acted as an EC-specific GEF to mediate VEGF-induced Cdc42 activation and potentiated RhoJ inactivation, thereby promoting actin polymerization and cell motility. Disruption of the Arhgef15 gene led to delayed extension of vascular networks and subsequent reduction of total vessel areas in postnatal mouse retinas. CONCLUSIONS/SIGNIFICANCE: Our study provides information useful to the development of new means of selectively manipulating angiogenesis without affecting homeostasis in un-targeted tissues; not only in eyes but also in various disease settings such as cancer.
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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.