ArticleFrontiers in pharmacology2017
Dickkopf-3 Upregulates VEGF in Cultured Human Endothelial Cells by Activating Activin Receptor-Like Kinase 1 (ALK1) Pathway.
Article in Frontiers in pharmacology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 26 citations in OpenAlex.
- Regulatory roles of non-coding and exosomal RNAs in colorectal cancer: spotlight on angiogenesis.Clinical and experimental medicine · 2025Review
- Distinct transcriptional regulation of the Wnt and TGFβ signaling families associated with wound healing and fibrotic outcomes to lens injury.Experimental eye research · 2025Article
- Unraveling the Multifaceted Role of the miR-17-92 Cluster in Colorectal Cancer: From Mechanisms to Biomarker Potential.Current issues in molecular biology · 2024Review
- miR-4739 promotes epithelial-mesenchymal transition and angiogenesis in "driver gene-negative" non-small cell lung cancer via activating the Wnt/β-catenin signaling.Cellular oncology (Dordrecht, Netherlands) · 2023Article
- CD31 defines a subpopulation of human adipose-derived regenerative cells with potent angiogenic effects.Scientific reports · 2023Article
- Interventions to Address Cardiovascular Risk in Obese Patients: Many Hands Make Light Work.Journal of cardiovascular development and disease · 2023Review
- Novel extracellular role of REIC/Dkk-3 protein in PD-L1 regulation in cancer cells.Journal of molecular medicine (Berlin, Germany) · 2023Article
- Review
- Combination of Ad-SGE-REIC and bevacizumab modulates glioma progression by suppressing tumor invasion and angiogenesis.PloS one · 2022Article
- miR-1290 contributes to oncogenesis and angiogenesis via targeting of THBS1, DKK3 and, SCAI.BioImpacts : BI · 2022Article
- Vitamin D sufficiency enhances differentiation of patient-derived prostate epithelial organoids.iScience · 2021Article
- The role of Wnt signalling in development of coronary artery disease and its risk factors.Open biology · 2020Review
- Pro-angiogenic Activity Discriminates Human Adipose-Derived Stromal Cells From Retinal Pericytes: Considerations for Cell-Based Therapy of Diabetic Retinopathy.Frontiers in cell and developmental biology · 2020Article
- Angioregulatory microRNAs in Colorectal Cancer.Cancers · 2019Review
- FGF21 Protects Against Hypoxia Injury Through Inducing HSP72 in Cerebral Microvascular Endothelial Cells.Frontiers in pharmacology · 2019Article
- Protective effect of stromal Dickkopf-3 in prostate cancer: opposing roles for TGFBI and ECM-1.Oncogene · 2018Article
- Dickkopf-3 Causes Neuroprotection by Inducing Vascular Endothelial Growth Factor.Frontiers in cellular neuroscience · 2018Article
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
Dkk-3 is a member of the dickkopf protein family of secreted inhibitors of the Wnt pathway, which has been shown to enhance angiogenesis. The mechanism underlying this effect is currently unknown. Here, we used cultured HUVECs to study the involvement of the TGF-β and VEGF on the angiogenic effect of Dkk-3. Addition of hrDkk-3 peptide (1 or 10 ng/ml) to HUVECs for 6 or 12 h enhanced the intracellular and extracellular VEGF protein levels, as assessed by RTPCR, immunoblotting, immunocytochemistry and ELISA. The increase in the extracellular VEGF levels was associated to the VEGFR2 activation. Pharmacological blockade of VEGFR2 abrogated Dkk-3-induced endothelial cell tubes formation, indicating that VEGF is a molecular player of the angiogenic effects of Dkk-3. Moreover, Dkk-3 enhanced Smad1/5/8 phosphorylation and recruited Smad4 to the VEGF gene promoter, suggesting that Dkk-3 activated ALK1 receptor leading to a transcriptional activation of VEGF. This mechanism was instrumental to the increased VEGF expression and endothelial cell tubes formation mediated by Dkk-3, because both effects were abolished by siRNA-mediated ALK1 knockdown. In summary, we have found that Dkk-3 activates ALK1 to stimulate VEGF production and induce angiogenesis in HUVECs.
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