Differential gene expression in SAEC and HMVEC grown in monoculture or coculture and exposed to MWCNT: correlation with in vivo Studies.
Talkington-B; Dong-C; Zhao-X; Dymacek-J; Castranova-V; Qian-Y; Guo-NL
Toxicologist 2014 Mar; 138(1):155
In vitro coculture systems are at the forefront of molecular research due to their increased ability for cell-cell communication. In this study, small airway epithelial cells (SAEC) and human microvascular endothelial cells (HMVEC) were grown separately in monoculture or together in an alveolar-capillary coculture and exposed to either dispersion media control or multi-walled carbon nanotubes (MWCNT) for 6 or 24 h. Global mRNA profiling determined genes that were differentially expressed in coculture as compared to monoculture, and Ingenuity Pathway Analysis determined the biological functions and related pathways of these genes. A total of 1505 SAEC and 54 HMVEC genes, commonly involved in the cell cycle and cell proliferation, were differentially expressed in control coculture experiments as compared to monoculture (SAM 1%, FC >1.5). A total of 1601 SAEC and 2016 HMVEC genes, commonly involved in cell movement and survival, were differentially expressed in coculture as compared to monoculture following MWCNT exposure (SAM 1%, FC >1.5). A correlation study of gene expression between monoculture, coculture, and in vivo gene expression from mice lungs exposed to MWCNT determined that coculture gene expression had a better correlation with in vivo gene expression than monoculture. In this study, we determined that gene expression in cells from coculture models is different from expression in the corresponding cells in monoculture. As coculture gene expression better correlates with gene expression seen in vivo, we hypothesize that coculture may offer an enhanced in vitro model for nanoparticle risk assessment.
Toxicology; Cell-function; Cellular-function; Cell-damage; Nanotechnology; Lung; Exposure-levels; Pulmonary-disorders; Pulmonary-function; Pulmonary-system; Pulmonary-system-disorders; Molecular-structure; In-vivo-study; Molecular-biology; Molecular-structure
The Toxicologist. Society of Toxicology 53rd Annual Meeting and ToxExpo, March 23-27, 2014, Phonex, Arizona