ArticleMolecular biology reports2020
IGF-binding proteins 3 and 4 are regulators of sprouting angiogenesis.
Article in Molecular biology reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 28 citations in OpenAlex.
- Leveraging IGF signaling to improve the spatial organization and regenerative potential of iPSC-derived vascularized liver organoids.Science advances · 2026Article
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- Cell phenotypic conversion and fate change during the host defense response, tissue injury and repair.Pharmacology & therapeutics · 2026Review
- Mechanism of Yiqi Huoxue Granule in promoting angiogenesis of skin lesion tissue by increasing CSF2 to reduce mesenchymal stem cell apoptosis.Frontiers in pharmacology · 2026Article
- Pathologic Signaling and Disease Implications of Insulin-like Growth Factor Binding Proteins in Cancer, Cardiovascular Disease, and Fibrosis.International journal of molecular sciences · 2025Review
- Extracellular matrix ligands modulate the endothelial progenitor cell secretome for enhanced angiogenesis.Acta biomaterialia · 2025Article
- In-silico analysis predicts disruption of normal angiogenesis as a causative factor in osteoporosis pathogenesis.BMC genomic data · 2024Article
- Culturing Conditions Dictate the Composition and Pathways Enrichment of Human and Rat Perirenal Adipose-Derived Stromal Cells' Secretomes.Stem cell reviews and reports · 2024Article
- New Insights in ATP Synthesis as Therapeutic Target in Cancer and Angiogenic Ocular Diseases.The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society · 2024Review
- Single cell atlas of kidney cancer endothelial cells reveals distinct expression profiles and phenotypes.BJC reports · 2024Article
- Motor neurons and endothelial cells additively promote development and fusion of human iPSC-derived skeletal myocytes.Skeletal muscle · 2024Article
- CDK12 regulates angiogenesis of advanced prostate cancer by IGFBP3.International journal of oncology · 2024Article
- Single cell atlas of kidney cancer endothelial cells reveals distinct expression profiles and phenotypes.Research square · 2023Article
- Understanding tumour endothelial cell heterogeneity and function from single-cell omics.Nature reviews. Cancer · 2023Review
- Effect of insulin-like growth factor system on luteinising angiogenesis.Reproduction & fertility · 2023Article
- Maternal plasma proteome profiling of biomarkers and pathogenic mechanisms of early-onset and late-onset preeclampsia.Scientific reports · 2022Article
- Review
- Genome-wide promoter methylation profiling in a cellular model of melanoma progression reveals markers of malignancy and metastasis that predict melanoma survival.Clinical epigenetics · 2022Article
- Endothelial Dysfunction in the Context of Blood-Brain Barrier Modeling.Journal of evolutionary biochemistry and physiology · 2022Article
- Issues of origin, morphology and clinical significance of tumor microvessels in gastric cancer.World journal of gastroenterology · 2021Review
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 3 countries.
Funding
Abstract
purposeWe have previously identified insulin-like growth factor 2 (IGF2) and insulin-like growth factor 1 receptor (IGF1R) as essential proteins for tip cell maintenance and sprouting angiogenesis. In this study, we aim to identify other IGF family members involved in endothelial sprouting angiogenesis.
methodsEffects on sprouting were analyzed in human umbilical vein endothelial cells (HUVECs) using the spheroid-based sprouting model, and were quantified as mean number of sprouts per spheroid and average sprout length. RNA silencing technology was used to knockdown gene expression. Recombinant forms of the ligands (IGF1 and IGF2, insulin) and the IGF-binding proteins (IGFBP) 3 and 4 were used to induce excess effects. Effects on the tip cell phenotype were analyzed by measuring the fraction of CD34
resultsKnockdown of IGF2 inhibited sprouting in HUVECs, in particular when cultured in the absence of serum, suggesting that components in serum influence the signaling of IGF2 in angiogenesis in vitro. We then determined the effects of IGFBP3 and IGFBP4, which are both present in serum, on IGF2-IGF1R signaling in sprouting angiogenesis in the absence of serum: knockdown of IGFBP3 significantly reduced sprouting angiogenesis, whereas knockdown of IGFBP4 resulted in increased sprouting angiogenesis in both flow cytometry analysis and immunohistochemical analysis of the 3D angiogenesis model. Other IGF family members except INSR did not affect IGF2-IGF1R signaling.
conclusionsSerum components and IGF binding proteins regulate IGF2 effects on sprouting angiogenesis. Whereas IGFBP3 acts as co-factor for IGF2-IGF1R binding, IGFBP4 inhibits IGF2 signaling.
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