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Proteomic Analysis of Endothelial Cells Exposed to Ultrasmall Nanoparticles Reveals Disruption in Paracellular and Transcellular Transport
Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Division of Hematopoiesis and Developmental Biology.
Stockholm Univ, Sweden.
Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Univ Basque Country, Spain.ORCID iD: 0000-0002-3894-2218
2019 (English)In: Proteomics, ISSN 1615-9853, E-ISSN 1615-9861, Vol. 19, no 5, article id 1800228Article in journal (Refereed) Published
Abstract [en]

The large interactive surfaces of nanoparticles (NPs) increase the opportunities to develop NPs for vascular targeting. Proteomic analysis of endothelial cells exposed to NPs reveals the cellular response and turns the focus into the impairment of the endothelial permeability. Here, quantitative proteomics and transcriptome sequencing are combined to evaluate the effects of exposure to sub-lethal concentrations of TiO2-USNPs and TiO2-NPs on human dermal microvascular endothelial cells. Endothelial cells react to preserve the semi-permeable properties that are essential for vascular tissue fluid homeostasis, vascular development, and angiogenesis. The main impact of the exposure was alteration of functional complexes involved in cell adhesion, vesicular transport, and cytoskeletal structure. Those are the core cellular structures that are linked to the permeability and the integrity of the endothelial tissue. Moreover, the extracellular proteins uptake along wih the NPs into the endothelial cells escape the lysosomal degradation pathway. These findings improve the understanding of the interaction of NPs with endothelial cell. The effects of the studied NPs modulating cell-cell adhesion and vesicular transport can help to evaluate the distribution of NPs via intravenous administration.

Place, publisher, year, edition, pages
WILEY , 2019. Vol. 19, no 5, article id 1800228
Keywords [en]
endothelial cells; nanoparticles; paracellular; proteomics; RNA-seq; transcellular transport; ultrasmall nanoparticles
National Category
Cell and Molecular Biology
Identifiers
URN: urn:nbn:se:liu:diva-155548DOI: 10.1002/pmic.201800228ISI: 000460194400007PubMedID: 30632670OAI: oai:DiVA.org:liu-155548DiVA, id: diva2:1299392
Note

Funding Agencies|Swedish Research Council-Natural Science, VR-NT; FORMAS; Carl Trygger Foundation; Oscar and Lilli Lamms Minne Foundation; Magnus Bergvall Foundation; Angpanneforening Research foundation; VINNOVA; County Council of Ostergotland, Sweden; IKER-BASQUE, Basque Country foundation for science; Linkoping University, Sweden

Available from: 2019-03-26 Created: 2019-03-26 Last updated: 2020-04-28

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