Dataset Information

Identification of genes implicated in methapyrilene-induced hepatotoxicity by comparing differential gene expression in target and nontarget tissue.

ABSTRACT:

Background

Toxicogenomics experiments often reveal thousands of transcript alterations that are related to multiple processes, making it difficult to identify key gene changes that are related to the toxicity of interest.

Objectives

The objective of this study was to compare gene expression changes in a nontarget tissue to the target tissue for toxicity to help identify toxicity-related genes.

Methods

Male rats were given the hepatotoxicant methapyrilene at two dose levels, with livers and kidneys removed 24 hr after one, three, and seven doses for gene expression analysis. To identify gene changes likely to be related to toxicity, we analyzed genes on the basis of their temporal pattern of change using a program developed at the National Institute of Environmental Health Sciences, termed "EPIG" (extracting gene expression patterns and identifying co-expressed genes).

Results

High-dose methapyrilene elicited hepatic damage that increased in severity with the number of doses, whereas no treatment-related lesions were observed in the kidney. High-dose methapyrilene elicited thousands of gene changes in the liver at each time point, whereas many fewer gene changes were observed in the kidney. EPIG analysis identified patterns of gene expression correlated to the observed toxicity, including genes associated with endoplasmic reticulum stress and the unfolded protein response.

Conclusions

By factoring in dose level, number of doses, and tissue into the analysis of gene expression elicited by methapyrilene, we were able to identify genes likely to not be implicated in toxicity, thereby allowing us to focus on a subset of genes to identify toxicity-related processes.

SUBMITTER: Auman JT

PROVIDER: S-EPMC1852695 | biostudies-literature | 2007 Apr

REPOSITORIES: biostudies-literature

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Publications

Identification of genes implicated in methapyrilene-induced hepatotoxicity by comparing differential gene expression in target and nontarget tissue.

Auman J Todd JT Chou Jeff J Gerrish Kevin K Huang Qihong Q Jayadev Supriya S Blanchard Kerry K Paules Richard S RS

Environmental health perspectives 20070117 4

<h4>Background</h4>Toxicogenomics experiments often reveal thousands of transcript alterations that are related to multiple processes, making it difficult to identify key gene changes that are related to the toxicity of interest.<h4>Objectives</h4>The objective of this study was to compare gene expression changes in a nontarget tissue to the target tissue for toxicity to help identify toxicity-related genes.<h4>Methods</h4>Male rats were given the hepatotoxicant methapyrilene at two dose levels, ...[more]

PMID: 17450226

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Project description:BACKGROUND:MiRNAs (microRNA) are 18-24?nt endogenous noncoding RNAs that regulate gene expression at the post-transcriptional level, including tissue-specific, developmental timing and evolutionary conservation gene expression. RESULTS:This study used high-throughput sequencing technology for the first time in Larix olgensis, predicted 78 miRNAs, including 12,229,003 reads sRNA, screened differentially expressed miRNAs. Predicting target genes was helpful for understanding the miRNA regulation function and obtained 333 corresponding target genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional annotation were analysed, mostly including nucleic acid binding, plant hormone signal transduction, pantothenate and CoA biosynthesis, and cellulose synthase. This study will lay the foundation for clarifying the complex miRNA-mediated regulatory network for growth and development. In view of this, spatio-temporal expression of miR396, miR950, miR164, miR166 and miR160 were analysed in Larix olgensis during the growth stages of not lignified, beginning of lignification, and completely lignified in different tissues (root, stem, and leaf) by quantitative real-time PCR (qRT-PCR). There were differences in the expression of miRNAs in roots, stems and leaves in the same growth period. At 60?days, miR160, miR166 and miR396-2 exhibited the highest expression in leaves. At 120?days, most miRNAs in roots and stems decreased significantly. At 180?days, miRNAs were abundantly expressed in roots and stems. Meanwhile, analysis of the expression of miRNAs in leaves revealed that miR396-2 was reduced as time went on, whereas other miRNAs increased initially and then decreased. On the other hand, in the stems, miR166-1 was increase, whereas other miRNAs, especially miR160, miR164, miR396 and miR950-1, first decreased and then increased. Similarly, in the roots, miR950-2 first decreased and then increased, whereas other miRNAs exhibited a trend of continuous increase. CONCLUSIONS:The present investigation included rapid isolation and identification of miRNAs in Larix olgensis through construction of a sRNA library using Solexa and predicted 78 novel miRNAs, which showed differential expression levels in different tissues and stages. These results provided a theoretical basis for further revealing the genetic regulation mechanism of miRNA in the growth and development of conifers and the verification of function in target genes.

Dataset Information

Identification of genes implicated in methapyrilene-induced hepatotoxicity by comparing differential gene expression in target and nontarget tissue.

Background

Objectives

Methods

Results

Conclusions

Publications

Identification of genes implicated in methapyrilene-induced hepatotoxicity by comparing differential gene expression in target and nontarget tissue.

Similar Datasets

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