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| Status |
Public on Sep 19, 2011 |
| Title |
Alterations in Gene Expression in Human Mesothelial Cells Correlate with Mineral Pathogenicity |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Human mesothelial cells (LP9/TERT-1) were exposed to low and high (15 and 75 μm2/cm2 dish) equal surface area concentrations of crocidolite asbestos, nonfibrous talc, fine titanium dioxide (TiO2), or glass beads for 8 or 24 h. RNA was then isolated for Affymetrix microarrays, GeneSifter analysis and QRT-PCR. Gene changes by asbestos were concentration- and time-dependent. At low nontoxic concentrations, asbestos caused significant changes in mRNA expression of 29 genes at 8 h and 205 genes at 24 h, whereas changes in mRNA levels of 236 genes occurred in cells exposed to high concentrations of asbestos for 8 h. Human primary pleural mesothelial cells also showed the same patterns of increased gene expression by asbestos. Nonfibrous talc at low concentrations in LP9/TERT-1 mesothelial cells caused increased expression of 1 gene Activating Transcription Factor 3 (ATF3) at 8 h and no changes at 24 h, whereas expression levels of 30 genes were elevated at 8 h at high talc concentrations. Fine TiO2 or glass beads caused no changes in gene expression. In human ovarian epithelial (IOSE) cells, asbestos at high concentrations elevated expression of 2 genes (NR4A2, MIP2) at 8 h and 16 genes at 24 h that were distinct from those elevated in mesothelial cells. Since ATF3 was the most highly expressed gene by asbestos, its functional importance in cytokine production by LP9/TERT-1 cells was assessed using siRNA approaches. Results reveal that ATF3 modulates production of inflammatory cytokines (IL-1β, IL-13, G-CSF) and growth factors (VEGF and PDGF-BB) in human mesothelial cells.
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| Overall design |
Microarrays were performed on samples from 3 independent experiments. All cell types, time points, and mineral types and concentrations were included in all 3 experiments. For each experiment, n=3 dishes were pooled into one sample per treatment group. Each of the pooled samples was analyzed on a separate array, i.e., n=3 arrays per condition (3 independent biological replicates). We tested the hypothesis that alteration in gene expression in human cells correlate with mineral pathogenicity. We used GeneSifter program to analyze our data and pairwise analysis showed that number of gene changes correlate with toxicity of pathogenic minerals. While non-pathogenic minerals glass beads and fine TiO2 treatment to cell resulted in no gene change, crocidolite asbestos caused maximum number of gene changes followed by talc.
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| Contributor(s) |
Shukla A, MacPherson M, Hillegass J, Ramos-Nino M, Alexeeva V, Vacek P, Bond J, Pass H, Steele C, Mossman B |
| Citation(s) |
19097984 |
| Submission date |
Dec 18, 2008 |
| Last update date |
Dec 06, 2018 |
| Contact name |
Jeffrey P Bond |
| Organization name |
University of Vermont
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| Department |
Microbiology and Molecular Genetics
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| Street address |
95 Carrigan Dri e
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| City |
Burlington |
| State/province |
VT |
| ZIP/Postal code |
05405 |
| Country |
USA |
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| Platforms (1) |
| GPL571 |
[HG-U133A_2] Affymetrix Human Genome U133A 2.0 Array |
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| Samples (57)
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| Relations |
| BioProject |
PRJNA112389 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE14034_RAW.tar |
117.1 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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