Exposure to Zinc Oxide Nanoparticles Disrupts Endothelial Tight and Adherens Junctions and Induces Pulmonary Inflammatory Cell Infiltration

Chen, Chen-Mei; Wu, Meng-Ling; Ho, Yen-Chun; Gung, Pei-Yu; Tsai, Ming-Hsien; Orekhov, Alexander N.; Sobenin, Igor A.; Lin, Pinpin; Yet, Shaw-Fang

doi:10.3390/ijms21103437

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Exposure to Zinc Oxide Nanoparticles Disrupts Endothelial Tight and Adherens Junctions and Induces Pulmonary Inflammatory Cell Infiltration

¹,

¹,

²,

⁴

^2,*

and

Shaw-Fang Yet

^1,5,*

Institute of Cellular and System Medicine, National Health Research Institutes, Zhunan 35053, Taiwan

National Institute of Environmental Health Sciences, National Health Research Institutes, Zhunan 35053, Taiwan

Institute of Human Morphology, 3 Tsyurupa Street, Moscow 117418, Russia

⁴

Laboratory of Medical Genetics, National Medical Research Center of Cardiology, 15A 3-rd Cherepkovskaya Street, Moscow 121552, Russia

⁵

Graduate Institute of Biomedical Sciences, China Medical University, Taichung 40402, Taiwan

Authors to whom correspondence should be addressed.

Int. J. Mol. Sci. 2020, 21(10), 3437; https://doi.org/10.3390/ijms21103437

Received: 8 April 2020 / Revised: 27 April 2020 / Accepted: 11 May 2020 / Published: 13 May 2020

(This article belongs to the Section Molecular Biology)

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Abstract

Zinc oxide nanoparticles (ZnONPs) are frequently encountered nanomaterials in our daily lives. Despite the benefits of ZnONPs in a variety of applications, many studies have shown potential health hazards of exposure to ZnONPs. We have shown that oropharyngeal aspiration of ZnONPs in mice increases lung inflammation. However, the detailed mechanisms underlying pulmonary inflammatory cell infiltration remain to be elucidated. Endothelium functions as a barrier between the blood stream and the blood vessel wall. Endothelial barrier dysfunction may increase infiltration of immune cells into the vessel wall and underlying tissues. This current study examined the effects of ZnONPs exposure on endothelial barriers. ZnONPs exposure increased leukocyte infiltration in the mouse lungs. In endothelial cells, ZnONPs reduced the continuity of tight junction proteins claudin-5 and zonula occludens-1 (ZO-1) at the cell junctions. ZnONPs induced adherens junction protein VE-cadherin internalization from membrane to cytosol and dissociation with β-catenin, leading to reduced and diffused staining of VE-cadherin and β-catenin at cell junctions. Our results demonstrated that ZnONPs disrupted both tight and adherens junctions, compromising the integrity and stability of the junction network, leading to inflammatory cell infiltration. Thus, ZnONPs exposure in many different settings should be carefully evaluated for vascular effects and subsequent health impacts. View Full-Text

Keywords: zinc oxide nanoparticles; pulmonary infiltration; endothelial barrier; tight junctions; adherens junctions

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Chen, C.-M.; Wu, M.-L.; Ho, Y.-C.; Gung, P.-Y.; Tsai, M.-H.; Orekhov, A.N.; Sobenin, I.A.; Lin, P.; Yet, S.-F. Exposure to Zinc Oxide Nanoparticles Disrupts Endothelial Tight and Adherens Junctions and Induces Pulmonary Inflammatory Cell Infiltration. Int. J. Mol. Sci. 2020, 21, 3437. https://doi.org/10.3390/ijms21103437

AMA Style

Chen C-M, Wu M-L, Ho Y-C, Gung P-Y, Tsai M-H, Orekhov AN, Sobenin IA, Lin P, Yet S-F. Exposure to Zinc Oxide Nanoparticles Disrupts Endothelial Tight and Adherens Junctions and Induces Pulmonary Inflammatory Cell Infiltration. International Journal of Molecular Sciences. 2020; 21(10):3437. https://doi.org/10.3390/ijms21103437

Chicago/Turabian Style

Chen, Chen-Mei, Meng-Ling Wu, Yen-Chun Ho, Pei-Yu Gung, Ming-Hsien Tsai, Alexander N. Orekhov, Igor A. Sobenin, Pinpin Lin, and Shaw-Fang Yet. 2020. "Exposure to Zinc Oxide Nanoparticles Disrupts Endothelial Tight and Adherens Junctions and Induces Pulmonary Inflammatory Cell Infiltration" International Journal of Molecular Sciences 21, no. 10: 3437. https://doi.org/10.3390/ijms21103437

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Exposure to Zinc Oxide Nanoparticles Disrupts Endothelial Tight and Adherens Junctions and Induces Pulmonary Inflammatory Cell Infiltration

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