ArticleFrontiers in physiology2019
Axon Guidance-Related Factor FLRT3 Regulates VEGF-Signaling and Endothelial Cell Function.
Article in Frontiers in physiology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 24 citations in OpenAlex.
- From genes to diagnosis: The impact of UNC5B and DOK5 in intracranial aneurysm detection and pathogenesis.PloS one · 2026Article
- miR-144-3p targeting FLRT3 in osteogenic differentiation of mandibular bone marrow mesenchymal stem cells.Human genomics · 2025Article
- Article
- Circular RNA-Encoded Proteins in Disease Pathogenesis.International journal of biological sciences · 2025Review
- Vascular FLRT2 regulates venous-mediated angiogenic expansion and CNS barriergenesis.Nature communications · 2024Article
- A protein-encoding CCDC7 circular RNA inhibits the progression of prostate cancer by up-regulating FLRT3.NPJ precision oncology · 2024Article
- FOXG1 drives transcriptomic networks to specify principal neuron subtypes during the development of the medial pallium.Science advances · 2023Article
- Effective oxygen metabolism-based prognostic signature for colorectal cancer.Frontiers in oncology · 2023Article
- Tumor-specific interendothelial adhesion mediated by FLRT2 facilitates cancer aggressiveness.The Journal of clinical investigation · 2022Article
- Expression Profile of Genes Encoding Proteins Involved in Regulation of Vasculature Development and Heart Muscle Morphogenesis-A Transcriptomic Approach Based on a Porcine Model.International journal of molecular sciences · 2021Article
- Functionalizing biomaterials to promote neurovascular regeneration following skeletal muscle injury.American journal of physiology. Cell physiology · 2021Review
- Expression of FLRT2 in Postnatal Central Nervous System Development and After Spinal Cord Injury.Frontiers in molecular neuroscience · 2021Article
- UNC5B Promotes Vascular Endothelial Cell Senescence via the ROS-Mediated P53 Pathway.Oxidative medicine and cellular longevity · 2021Article
- Rare genetic variants suggest dysregulation of signaling pathways in low- and high-risk patients developing severe ovarian hyperstimulation syndrome.Journal of assisted reproduction and genetics · 2020Article
- Heme Oxygenase-1 Upregulation: A Novel Approach in the Treatment of Cardiovascular Disease.Antioxidants & redox signaling · 2020Review
- Positive Effects of Heme Oxygenase Upregulation on Adiposity and Vascular Dysfunction: Gene Targeting vs. Pharmacologic Therapy.International journal of molecular sciences · 2019Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Vascular endothelial growth factors (VEGFs) are key mediators of endothelial cell (EC) function in angiogenesis. Emerging knowledge also supports the involvement of axon guidance-related factors in the regulation of angiogenesis and vascular patterning. In the current study, we demonstrate that fibronectin and leucine-rich transmembrane protein-3 (FLRT3), an axon guidance-related factor connected to the regulation of neuronal cell outgrowth and morphogenesis but not to VEGF-signaling, was upregulated in ECs after VEGF binding to VEGFR2. We found that FLRT3 exhibited a transcriptionally paused phenotype in non-stimulated human umbilical vein ECs. After VEGF-stimulation its nascent RNA and mRNA-levels were rapidly upregulated suggesting that the regulation of FLRT3 expression is mainly occurring at the level of transcriptional elongation. Blockage of FLRT3 by siRNA decreased survival of ECs and their arrangement into capillary-like structures but enhanced cell migration and wound closure in wound healing assay. Bifunctional role of FLRT3 in repulsive vs. adhesive cell signaling has been already detected during embryogenesis and neuronal growth, and depends on its interactions either with UNC5B or another FLRT3 expressed by adjacent cells. In conclusion, our findings demonstrate that besides regulating neuronal cell outgrowth and morphogenesis, FLRT3 has a novel role in ECs via regulating VEGF-stimulated EC-survival, migration, and tube formation. Thus, FLRT3 becomes a new member of the axon guidance-related factors which participate in the VEGF-signaling and regulation of the EC functions.
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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.