Silver nanoparticles alter epithelial basement membrane integrity, cell adhesion molecule expression, and TGF-β1 secretion

Megan E Martin; Denise K Reaves; Breanna Jeffcoat; Jeffrey R Enders; Lindsey M Costantini; Susan T Yeyeodu; Diane Botta; Terrance J Kavanagh; Jodie M Fleming

doi:10.1016/j.nano.2019.102070

Silver nanoparticles alter epithelial basement membrane integrity, cell adhesion molecule expression, and TGF-β1 secretion

Nanomedicine. 2019 Oct:21:102070. doi: 10.1016/j.nano.2019.102070. Epub 2019 Jul 24.

Authors

Megan E Martin¹, Denise K Reaves¹, Breanna Jeffcoat¹, Jeffrey R Enders², Lindsey M Costantini¹, Susan T Yeyeodu³, Diane Botta⁴, Terrance J Kavanagh⁴, Jodie M Fleming⁵

Affiliations

¹ Department of Biological and Biomedical Sciences, North Carolina Central University, Durham, NC, USA.
² Molecular Education, Technology and Research Innovation Center, North Carolina State University, Raleigh, NC, USA; Center for Human Health and the Environment, North Carolina State University, Raleigh, NC, USA.
³ Charles River Discovery Services, Morrisville, NC, USA.
⁴ Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA, USA.
⁵ Department of Biological and Biomedical Sciences, North Carolina Central University, Durham, NC, USA; Center for Human Health and the Environment, North Carolina State University, Raleigh, NC, USA; Lineberger Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. Electronic address: Jodie.fleming@nccu.edu.

Abstract

Silver nanoparticles (AgNPs) are widely used in consumer and pharmaceutical products due to their antipathogenic properties. However, safety concerns have been raised due to their bioactive properties. While reports have demonstrated AgNPs can embed within the extracellular matrix, their effects on basement membrane (BM) production, integrin engagement, and tissue-integrity are not well-defined. This study analyzed the effects of AgNPs on BM production, composition and integrin/focal adhesion interactions in representative lung, esophageal, breast and colorectal epithelia models. A multidisciplinary approach including focused proteomics, QPCR arrays, pathway analyses, and immune-based, structural and functional assays was used to identify molecular and physiological changes in cell adhesions and the BM induced by acute and chronic AgNP exposure. Dysregulated targets included CD44 and transforming growth factor-beta, two proteins frequently altered during pathogenesis. Results indicate AgNP exposure interferes with BM and cell adhesion dynamics, and provide insight into the mechanisms of AgNP-induced disruption of epithelial physiology.

Keywords: Basement membrane; CD44; Epithelial cells; Extracellular matrix; Silver nanoparticles; Transforming growth factor-beta.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Basement Membrane / metabolism*
Cell Adhesion Molecules / biosynthesis*
Cell Line, Tumor
Gene Expression Regulation / drug effects*
Humans
Metal Nanoparticles / chemistry*
Silver* / chemistry
Silver* / pharmacology
Transforming Growth Factor beta1 / biosynthesis*

Substances

Cell Adhesion Molecules
TGFB1 protein, human
Transforming Growth Factor beta1
Silver

Abstract

Publication types

MeSH terms

Substances

Grants and funding