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

• Published in: Nanomedicine Vol. 21; p. 102070
• Main Authors: Martin, Megan E., Reaves, Denise K., Jeffcoat, Breanna, Enders, Jeffrey R, Costantini, Lindsey M., Yeyeodu, Susan T., Botta, Diane, Kavanagh, Terrance J., Fleming, Jodie M.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.10.2019
• Subjects: Basement membrane; CD44; Epithelial cells; Extracellular matrix; Silver nanoparticles; Transforming growth factor-beta; Extracellular matrix; Transforming growth factor-beta; Epithelial cells; Silver nanoparticles; CD44; Basement membrane
• ISSN: 1549-9634; 1549-9642
• DOI: 10.1016/j.nano.2019.102070

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. The effect of silver nanoparticles (AgNP) on epithelial cell basement membrane (BM) production, composition and barrier integrity is not well-defined. BM-focused proteomics, quantitative PCR and pathway analysis identified specific acute and chronic AgNP-sensitive targets in normal lung, esophageal, colon and breast epithelial cell models. Immunological, functional and structural assays suggest caveolae-mediated AgNP uptake, loss of barrier function, altered collagen fiber organization and composition, and dysregulated CD44 and TGFβ all significantly modify epithelial physiology. [Display omitted]