RETRACTED ARTICLE: Gold nanoparticles inhibit vascular endothelial growth factor-induced angiogenesis and vascular permeability via Src dependent pathway in retinal endothelial cells
- 948 Downloads
The purpose of this study was to investigate the effect of gold nanoparticles on the signaling cascade related to angiogenesis and vascular permeability induced by Vascular Endothelial Growth Factor (VEGF) in Bovine retinal endothelial cells (BRECs). The effect of VEGF and gold nanoparticles on cell viability, migration and tubule formation was assessed. PP2 (Src Tyrosine Kinase inhibitor) was used as the positive control and the inhibitor assay was performed to compare the effect of AuNPs on VEGF induced angiogenesis. The transient transfection assay was performed to study the VEGFR2/Src activity during experimental conditions and was confirmed using western blot analysis. Treatment of BRECs with VEGF significantly increased the cell proliferation, migration and tube formation. Furthermore, gold nanoparticles (500 nM) significantly inhibited the proliferation, migration and tube formation, in the presence of VEGF in BRECs. The gold nanoparticles also inhibited VEGF induced Src phosphorylation through which their mode of action in inhibiting angiogenic pathways is revealed. The fate of the gold nanoparticles within the cells is being analyzed using the TEM images obtained. The potential of AuNPs to inhibit the VEGF165-induced VEGFR-2 phosphorylation is also being confirmed through the receptor assay which elucidates one of the possible mechanism by which AuNPs inhibit VEGF induced angiogenesis. These results indicate that gold nanoparticles can block VEGF activation of important signaling pathways, specifically Src in BRECs and hence modulation of these pathways may contribute to gold nanoparticles ability to block VEGF-induced retinal neovascularization.
KeywordsGold nanoparticles Src pathway VEGF Retinal neovascularization
The authors gratefully acknowledge Kyung Jin Lee, Department of Life Science, Cell Dynamics Research Centre, Gwangju Institute of Science and Technology, Gwangju 500-712, Republic of Korea for performing western blot analysis. The authors also wish to acknowledge the support of Dr. Puspha Viswanathan, Professor, Cancer Institute (WIA), Chennai, who helped us with TEM analysis. Prof G. Sangiliyandi was supported by grants from Council of Scientific and Industrial Research (CSIR), New Delhi (Project No. 37/0347) and Department of Science and Technology (DST), New Delhi (Project No. SR/NM/NS-31/2010), India. Mr. Kalishwaralal was supported by the grant for Senior Research Fellowship from Council of Scientific and Industrial Research (CSIR), New Delhi (Grant No. 9/1012(0003)2K10EMR-I), India.
- 46.Brown MT, Cooper JA (1996) Regulation, substrates and functions of src. Biochi Biophys Acta 1287:121–149Google Scholar