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.

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