ArticlePloS one2008
Foxc transcription factors directly regulate Dll4 and Hey2 expression by interacting with the VEGF-Notch signaling pathways in endothelial cells.
Article in PloS one, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 90 papers.
What it found
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Who cites it
90 citing papers in PubMed, 168 citations in OpenAlex.
- Mechanistic Insights into Maxing Shigan Decoction in Community-Acquired Pneumonia Based on Bioinformatics and Experimental Validation.Infection and drug resistance · 2026Article
- The role of notch signaling in tumor angiogenesis in hematological malignancies.Frontiers in oncology · 2026Review
- Crosstalk between endothelial cells and osteoblasts stimulates ALP via Notch signaling and RANKL/OPG ratio independently of Notch signaling in vitro.Cellular & molecular biology letters · 2025Article
- hsa-miR-5688 inhibits FOXC1-OCT4/SOX2 feedforward loop that drives chemoresistance in breast cancer stem cells.Molecular therapy. Oncology · 2025Article
- Exosomes Derived from Metformin-Pretreated BMSCs Accelerate Diabetic Wound Repair by Promoting Angiogenesis Via the LINC-PINT/miR-139-3p/FOXC2 Axis.Stem cell reviews and reports · 2025Article
- Role of cell rearrangement and related signaling pathways in the dynamic process of tip cell selection.Cell communication and signaling : CCS · 2024Review
- Transcription factors regulating vasculogenesis and angiogenesis.Developmental dynamics : an official publication of the American Association of Anatomists · 2024Review
- Transcriptional regulators of arterial and venous identity in the developing mammalian embryo.Current opinion in physiology · 2023Review
- PI(4,5)PScience advances · 2023Article
- Molecular Determinants of Chronic Venous Disease: A Comprehensive Review.International journal of molecular sciences · 2023Review
- Identification and characterization of enhancer elements controlling cell type-specific and signalling dependent chromatin programming during hematopoietic development.Stem cell investigation · 2023Review
- FOXO1 represses sprouty 2 and sprouty 4 expression to promote arterial specification and vascular remodeling in the mouse yolk sac.Development (Cambridge, England) · 2022Article
- Review
- Advanced Glycation End Products Induce Atherosclerosis via RAGE/TLR4 Signaling Mediated-M1 Macrophage Polarization-Dependent Vascular Smooth Muscle Cell Phenotypic Conversion.Oxidative medicine and cellular longevity · 2022Article
- The Notch Signaling Pathway Contributes to Angiogenesis and Tumor Immunity in Breast Cancer.Breast cancer (Dove Medical Press) · 2022Review
- Article
- Rebuilding the Vascular Network:Frontiers in cell and developmental biology · 2021Review
- The expression of AGGF1, FOXC2, and E-cadherin in esophageal carcinoma and their clinical significance.Medicine · 2020Article
- The Role of a Neurovascular Signaling Pathway Involving Hypoxia-Inducible Factor and Notch in the Function of the Central Nervous System.Biomolecules & therapeutics · 2020Review
- Endothelial cells on the move: dynamics in vascular morphogenesis and disease.Vascular biology (Bristol, England) · 2020Review
30 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
backgroundRecent studies have shown that in the developing embryo, arterial and venous identity is established by genetic mechanisms before circulation begins. Vascular endothelial growth factor (VEGF) signaling and its downstream Notch pathway play critical roles in arterial cell fate determination. We have recently shown that Foxc1 and Foxc2, two closely related Fox transcription factors, are essential for arterial cell specification during development by directly inducing the transcription of Delta-like 4 (Dll4), a ligand for Notch receptors. However, the basic mechanisms whereby the VEGF and Notch signaling pathways control transcriptional regulation of arterial-specific genes have yet to be elucidated. METHODOLOGIES/PRINCIPAL
findingsIn the current study, we examined whether and how Foxc transcription factors are involved in VEGF and Notch signaling in induction of Dll4 as well as the Notch target gene Hey2 in endothelial cells. We found that Foxc1 and Foxc2 directly activate the Hey2 promoter via Foxc binding elements. Significantly, Foxc2 physically and functionally interacts with a Notch transcriptional activation complex containing Su(H) and Notch intracellular domain to induce Hey2 promoter activity. Moreover, activation of the Dll4 and Hey2 promoters is induced by VEGF in conjunction with either Foxc1 or Foxc2 more than by either component alone. VEGF-activated PI3K and ERK intracellular pathways modulate the transcriptional activity of Foxc proteins in Dll4 and Hey2 induction. CONCLUSIONS/SIGNIFICANCE: Our new findings demonstrate that Foxc transcriptional factors interact with VEGF and Notch signaling to regulate arterial gene expression in multiple steps of the VEGF-Dll4-Notch-Hey2 signaling pathway.
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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.