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Title:IGF-binding proteins 3 and 4 are regulators of sprouting angiogenesis
Authors:ID Dallinga, Marchien G. (Author)
ID Habani, Yasmin I. (Author)
ID Kayser, Richelle P. (Author)
ID Noorden, Cornelis J. F. van (Author)
ID Klaassen, Ingeborg (Author)
ID Schlingemann, Reinier O. (Author)
Files:URL URL - Source URL, visit https://link.springer.com/article/10.1007/s11033-020-05339-0
 
.pdf PDF - Presentation file, download (2,16 MB)
MD5: 1B7C5E1382650835E5762AEB89F92361
 
Language:English
Typology:1.01 - Original Scientific Article
Organization:Logo NIB - National Institute of Biology
Abstract:Purpose We 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. Methods Effects 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+ tip cells using flow cytometry and immunohistochemistry in a 3D angiogenesis model. Experiments were performed in the presence and absence of serum. Results Knockdown 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. Conclusions Serum 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.
Keywords:Angiogenesis, tip cells, IGF2, IGF binding proteins, endothelial cells, cultured cells, endothelial growth factors
Publication status:Published
Publication version:Version of Record
Publication date:04.03.2020
Year of publishing:2020
Number of pages:str. 2561-2572
Numbering:Vol. 47
PID:20.500.12556/DiRROS-19551 New window
UDC:577
ISSN on article:0301-4851
DOI:10.1007/s11033-020-05339-0 New window
COBISS.SI-ID:40738565 New window
Publication date in DiRROS:23.07.2024
Views:446
Downloads:310
Metadata:XML DC-XML DC-RDF
:
DALLINGA, Marchien G., HABANI, Yasmin I., KAYSER, Richelle P., NOORDEN, Cornelis J. F. van, KLAASSEN, Ingeborg and SCHLINGEMANN, Reinier O., 2020, IGF-binding proteins 3 and 4 are regulators of sprouting angiogenesis. Molecular biology reports [online]. 2020. Vol. 47, p. 2561–2572. [Accessed 12 April 2025]. DOI 10.1007/s11033-020-05339-0. Retrieved from: https://dirros.openscience.si/IzpisGradiva.php?lang=eng&id=19551
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Record is a part of a journal

Title:Molecular biology reports
Shortened title:Mol. biol. rep.
Publisher:D. Reidel Publ. Co.
ISSN:0301-4851
COBISS.SI-ID:14135769 New window

Document is financed by a project

Funder:Other - Other funder or multiple funders
Funding programme:Rotterdamse Stichting Blindenbelangen
Project number:B20130006
Name:Grant
Funder:Other - Other funder or multiple funders
Funding programme:Stichting Nederlands Oogheelkundig Onderzoek
Project number:2013–04
Name:Grant
Funder:Other - Other funder or multiple funders
Funding programme:Landelijke Stichting voor Blinden en Slechtzienden
Funder:Other - Other funder or multiple funders
Funding programme:Algemene Nederlandse Vereniging Ter Voorkoming Van Bindheid
Funder:Other - Other funder or multiple funders
Funding programme:Stichting Blindenpenning
Funder:Other - Other funder or multiple funders
Funding programme:Novartisfonds
Funder:Other - Other funder or multiple funders
Funding programme:ODAS stichting
Project number:2013–12
Name:Grant UitZicht
Acronym:UitZicht

Licences

License:CC BY 4.0, Creative Commons Attribution 4.0 International
Link:http://creativecommons.org/licenses/by/4.0/
Description:This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.

Secondary language

Language:Slovenian
Keywords:biokemija, angiogeneza, celice, beljakovine


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