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Series GSE27023 Query DataSets for GSE27023
Status Public on Dec 02, 2011
Title Blood gene expression profile of control and crystalline silica exposed rats
Organism Rattus norvegicus
Experiment type Expression profiling by array
Summary The present research aimed to investigate peripheral blood gene expression profiling as a minimally invasive surrogate approach to study silica-induced pulmonary toxicity. Rats were exposed to crystalline silica by inhalation (15 mg/m3, 6 hours/day, 5 days). Pulmonary damage and blood gene expression profiles were determined at various latency periods (0 - 16 weeks). Silica exposure resulted in pulmonary toxicity and this was evidenced by histological changes in the lungs and elevation of LDH activity, and total protein and albumin contents in the bronchoalveolar lavage fluid (BALF) of the rats. Microarray analysis of global gene expression profiles in the blood of the rats identified genes that were differentially expressed in response to silica exposure and toxicity. The number of significantly differentially expressed genes in the blood of silica exposed rats correlated with the severity of silica-induced pulmonary toxicity. Genes involved in biological functions such as inflammatory response, cancer, pulmonary damage, oxidative stress, energy metabolism, fibrosis, etc, were found differentially expressed in the blood of the silica exposed rats compared with the controls. Induction of pulmonary inflammation in the silica exposed rats, as suggested by differential expression of inflammatory response genes in the blood, was supported by significant increases in the number of macrophages and infiltrating neutrophils as well as the activity of pro-inflammatory chemokines – MCP1 and MIP2, observed in the BALF of the silica exposed rats. A silica-responsive blood gene expression signature developed using the gene expression data predicted with significant accuracy the exposure of rats to lower concentrations (1 and 2 mg/m3) of silica. Taken together our findings suggest the potential application of peripheral blood gene expression profiling as a minimally invasive and efficient surrogate approach to detect and study silica-induced pulmonary toxicity.
 
Overall design 96 samples were analyzed in this experiment. The RNA from rat blood samples was isolated for gene expression studies. Rats (48) were exposed to crystalline silica by inhalation (15 mg/m3, 6 hours/day, 5 days) and air (24). Blood gene expression profiling was performed using rat blood samples, 8 each for silica exposed and 4 each for air exposed controls at various post-exposure time periods (0, 1, 2, 4, 8, and 16 weeks). A silica-responsive blood gene expression signature was developed using the gene expression data obtained from the 0 week post-exposure group and the control rats. The signature was tested for predicting silica exposure and resulting toxicity in the rats exposed to lower concentrations (1 and 2 mg/m3) of silica (8 rats per group) and air (8 rats).
 
Contributor(s) Sellamuthu R, Umbright C, Roberts J, Chapman R, Young S, Richardson D, Leonard H, McKinney W, Chen B, Frazer D, Li S, Kashon M, Joseph P
Citation(s) 21602193
Submission date Feb 02, 2011
Last update date Jul 29, 2014
Contact name Rajendran Sellamuthu
E-mail(s) rajsella@indiana.edu
Organization name National Institute for Occupational Safety and Health
Department HELD
Lab Molecular Carcinogenesis
Street address 1095 Willowdale Rd
City Morgantown
State/province WV
ZIP/Postal code 26505
Country USA
 
Platforms (1)
GPL6101 Illumina ratRef-12 v1.0 expression beadchip
Samples (96)
GSM665702 Blood_15mg silica, 8 week post-exposure_rep1
GSM665703 Blood_0mg silica, 4week post-exposure_rep2
GSM665704 Blood_15mg silica, 0 week post-exposure_rep1
Relations
BioProject PRJNA137691

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE27023_RAW.tar 2.8 Mb (http)(custom) TAR
GSE27023_non-normalized.txt.gz 25.5 Mb (ftp)(http) TXT
Raw data are available on Series record
Processed data included within Sample table

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