Abstract
Cooperation between VEGFR2 and integrin αVβ3 is critical for neovascularization in wound healing, cardiovascular ischemic diseases, ocular diseases, and tumor angiogenesis. In the present study, we developed a rule-based computational model to investigate the potential mechanism by which the Src-induced integrin association with VEGFR2 enhances VEGFR2 activation. Simulations demonstrated that the main function of integrin is to reduce the degradation of VEGFR2 and hence stabilize the activation signal. In addition, receptor synthesis rate and recruitment from internal compartment were found to be sensitive determinants of the activation state of VEGFR2. The model was then applied to simulate the effect of integrin-binding peptides such as tumstatin and cilengitide on VEGFR2 signaling. Further, computational modeling proposed potential molecular mechanisms for the angiogenesis-modulating activity of other integrin-binding peptides. The model highlights the complexity of the crosstalk between αVβ3 integrin and VEGFR2 and the necessity of utilizing models to elucidate potential mechanisms in angiogenesis-modulating peptide therapy.
Original language | English (US) |
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Pages (from-to) | 212-221 |
Number of pages | 10 |
Journal | Journal of Theoretical Biology |
Volume | 455 |
DOIs | |
State | Published - Oct 14 2018 |
Keywords
- Computational model
- Integrin signaling
- Mathematical model
- Systems biology
- VEGF
ASJC Scopus subject areas
- Statistics and Probability
- Modeling and Simulation
- General Biochemistry, Genetics and Molecular Biology
- General Immunology and Microbiology
- General Agricultural and Biological Sciences
- Applied Mathematics