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https://hdl.handle.net/10356/97752
Title: | Titanium dioxide nanomaterials cause endothelial cell leakiness by disrupting the homophilic interaction of VE–cadherin | Authors: | Tay, Chor Yong Chong, Han Chung Loo, Say Chye Joachim Leong, David Tai Wei Fang, W. Setyawati, M. I. Chia, S. L. Goh, S. L. Neo, M. J. Tan, S.M. Ng, K. W. Xie, J. P. Ong, C. N. Tan, N. S. |
Keywords: | DRNTU::Engineering::Materials::Nanostructured materials | Issue Date: | 2013 | Source: | Setyawati, M., Tay, C. Y., Chia, S., Goh, S., Fang, W., Neo, M., et al. (2013). Titanium dioxide nanomaterials cause endothelial cell leakiness by disrupting the homophilic interaction of VE–cadherin. Nature communications, 4, 1673-. | Series/Report no.: | Nature communications | Abstract: | The use of nanomaterials has raised safety concerns, as their small size facilitates accumulation in and interaction with biological tissues. Here we show that exposure of endothelial cells to TiO2 nanomaterials causes endothelial cell leakiness. This effect is caused by the physical interaction between TiO2 nanomaterials and endothelial cells’ adherens junction protein VE-cadherin. As a result, VE-cadherin is phosphorylated at intracellular residues (Y658 and Y731), and the interaction between VE-cadherin and p120 as well as β-catenin is lost. The resulting signalling cascade promotes actin remodelling, as well as internalization and degradation of VE-cadherin. We show that injections of TiO2 nanomaterials cause leakiness of subcutaneous blood vessels in mice and, in a melanoma-lung metastasis mouse model, increase the number of pulmonary metastases. Our findings uncover a novel non-receptor-mediated mechanism by which nanomaterials trigger intracellular signalling cascades via specific interaction with VE-cadherin, resulting in nanomaterial-induced endothelial cell leakiness. | URI: | https://hdl.handle.net/10356/97752 http://hdl.handle.net/10220/18159 |
ISSN: | 2041-1723 | DOI: | 10.1038/ncomms2655 | Schools: | School of Materials Science & Engineering School of Biological Sciences |
Fulltext Permission: | none | Fulltext Availability: | No Fulltext |
Appears in Collections: | SBS Journal Articles |
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