Arsenic exposure perturbs epithelial-mesenchymal cell transition and gene expression in a collagen gel assay

Alejandro Lencinas, Derrick M. Broka, Jay H. Konieczka, Scott E. Klewer, Parker B. Antin, Todd D. Camenisch, Raymond B. Runyan

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

Arsenic is a naturally occurring metalloid and environmental contaminant. Arsenic exposure in drinking water is reported to cause cancer of the liver, kidneys, lung, bladder, and skin as well as birth defects, including neural tube, facial, and vasculogenic defects. The early embryonic period most sensitive to arsenic includes a variety of cellular processes. One key cellular process is epithelial-mesenchymal transition (EMT) where epithelial sheets develop into three-dimensional structures. An embryonic prototype of EMT is found in the atrioventricular (AV) canal of the developing heart, where endothelia differentiate to form heart valves. Effects of arsenic on this cellular process were examined by collagen gel invasion assay (EMT assay) using explanted AV canals from chicken embryo hearts. AV canals treated with 12.5-500 ppb arsenic showed a loss of mesenchyme at 12.5 ppb, and mesenchyme formation was completely inhibited at 500 ppb. Altered gene expression in arsenic-treated explants was investigated by microarray analysis. Genes whose expression was altered consistently at exposure levels of 10, 25, and 100 ppb were identified, and results showed that 25 ppb in vitro was particularly effective. Three hundred and eighty two genes were significantly altered at this exposure level. Cytoscape analysis of the microarray data using the chicken interactome identified four clusters of altered genes based on published relationships and pathways. This analysis identified cytoskeleton and cell adhesion-related genes whose disruption is consistent with an altered ability to undergo EMT. These studies show that EMT is sensitive to arsenic and that an interactome-based approach can be useful in identifying targets.

Original languageEnglish (US)
Pages (from-to)273-285
Number of pages13
JournalToxicological Sciences
Volume116
Issue number1
DOIs
StatePublished - Mar 22 2010

Keywords

  • Cardiac toxicity
  • Cytoscape
  • EMT
  • Heart development
  • Interactome
  • Microarray

ASJC Scopus subject areas

  • Toxicology

Fingerprint Dive into the research topics of 'Arsenic exposure perturbs epithelial-mesenchymal cell transition and gene expression in a collagen gel assay'. Together they form a unique fingerprint.

  • Cite this