Cellular and Molecular Bioengineering

, Volume 8, Issue 3, pp 383–403 | Cite as

Quantification of VEGFRs, NRP1, and PDGFRs on Endothelial Cells and Fibroblasts Reveals Serum, Intra-Family Ligand, and Cross-Family Ligand Regulation

  • Si Chen
  • Xinyi Guo
  • Osazomon Imarenezor
  • P. I. Imoukhuede


Computational modeling of angiogenesis is limited by a lack of experimental data on angiogenic receptor levels. Recent receptor profiling quantified vascular endothelial growth factor receptors (VEGFRs); however data on other angiogenic receptors, such as platelet derived growth factor receptors (PDGFRs), are also necessary for the development of an accurate angiogenesis model. Here, we establish conditions for membrane PDGFR quantification. Additionally, we determine how several environmental conditions control membrane PDGFR levels on human dermal fibroblasts. We demonstrate that membrane PDGFRβ concentrations are negatively correlated with both media serum concentration and cell growth rate, in vitro. We also show VEGF-A165-mediated downregulation of membrane PDGFRα (~25%) and PDGFRβ (~30%), following a 24-h treatment. This supports the idea that VEGF-A165 acts independently of VEGFRs to signal through PDGFRα and PDGFRβ. We observe that PDGF-AA and PDGF-AB downregulate membrane PDGFRα by up to 55 and 75%, respectively, while having little to no effect on PDGFRβ or NRP1. We observe that PDGF-BB effects both PDGFRs and NRP1: membrane PDGFRα and PDGFRβ were downregulated by up to 70 and 90%, respectively, whereas membrane NRP1 was upregulated by up to 40%. These data provide the necessary insight to accurately represent PDGFRs in angiogenesis models, while offering new insight into the regulation of membrane PDGFRs.


Flow cytometry Cell-by-cell Angiogenesis Fibroblasts Endothelial cells Tyrosine kinase receptors 



Vascular endothelial growth factor receptor


Platelet derived growth factor receptor




Fibroblast growth factor


Transforming growth factor


Peripheral artery disease


Quantitative flow


Human dermal fibroblasts


Human umbilical vein endothelial cells


Fetal bovine serum


Dimethyl sulfoxide


Fibroblasts growth medium-2


Endothelial cell growth medium-2


Human recombinant basic fibroblast growth factor


Gentamicin and amphotericin diluted at a 11000 ratio


Dulbecco’s modified eagle medium





We would like to thank the American Cancer Society, Illinois Division Basic Research Grant, as well as the National Cancer Institute Grant for funding support. We would like to thank Audra Storm, Brendan Mathias, and Dipen Kumar for assistance with experiments, and Jared Weddell, Spencer Mamer, and Ali Ansari for insightful discussion. We also thank Marinos Kalafatis for careful and critical reading of the manuscript.

Conflict of interest

Si Chen, Xinyi Guo, Osazomon Imarenezor and PI Imoukhuede declare that they have no conflicts of interest.

Ethical Standards

No human studies or animal studies were carried out by the authors for this article.

Supplementary material

12195_2015_411_MOESM1_ESM.tif (306 kb)
Supplementary material 1 (TIFF 306 kb)
12195_2015_411_MOESM2_ESM.tif (167 kb)
Supplementary material 2 (TIFF 167 kb)
12195_2015_411_MOESM3_ESM.tif (704 kb)
Supplementary material 3 (TIFF 704 kb)


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Copyright information

© Biomedical Engineering Society 2015

Authors and Affiliations

  • Si Chen
    • 1
  • Xinyi Guo
    • 2
  • Osazomon Imarenezor
    • 3
  • P. I. Imoukhuede
    • 1
  1. 1.Bioengineering DepartmentUniversity of Illinois at Urbana-ChampaignChampaignUSA
  2. 2.Department of Molecular and Cellular BiologyUniversity of Illinois at Urbana-ChampaignChampaignUSA
  3. 3.Department of ChemistryUniversity of Illinois at Urbana-ChampaignChampaignUSA

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