 |
 |
GEO help: Mouse over screen elements for information. |
|
| Status |
Public on Aug 15, 2007 |
| Title |
Micro-RNAs in Adult Rat Liver are Refractory to Dioxin Treatment |
| Platform organisms |
Homo sapiens; Mus musculus; Rattus norvegicus |
| Sample organism |
Rattus norvegicus |
| Experiment type |
Non-coding RNA profiling by array
|
| Summary |
Dioxin-like chemicals are well-known for their ability to upregulate expression of numerous genes via the AH receptor (AHR). However, recent transcriptomic analyses in several laboratories indicate that dioxin-like chemicals or AHR genotype itself also can downregulate levels of mRNAs encoded by numerous genes. The mechanism responsible for such downregulation is unknown. We hypothesized that microRNAs (miRNAs), which have emerged as powerful negative regulators of mRNA levels in several systems, might be responsible for mRNA downregulation in dioxin/AHR pathways. We used the Exiqon miRNA array platform as well as quantitative RT-PCR to measure miRNA levels in dioxin-sensitive Long-Evans (Turku/AB; L-E) rats vs. dioxin-resistant Han/Wistar(Kuopio; H/W) rats. Treatment with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in vivo caused few changes in miRNA levels in rat livers and those changes that were statistically significant were of modest magnitude. AHR genotype had little effect on hepatic miRNA levels, either in constitutive expression or in response to TCDD – only a few miRNAs differed in expression between between L-E rats (that have wildtype AHR) compared to H/W rats (whose AHR has a large deletion in the transactivation domain). It is unlikely that mRNA downregulation by dioxins is mediated by miRNAs, nor are miRNAs likely to play a significant role in dioxin toxicity in adult rodent liver.
We conducted a thorough investigation to address the following questions: (1) does AHR genotype itself affect constitutive expression of microRNAs? (2) does TCDD affect microRNA levels and, if so, is this response dependent on the AHR? (3) does TCDD affect microRNA levels differently in animals that are sensitive to dioxin toxicity versus those that are dioxin-resistant? We assessed the in vivo effect of TCDD on microRNA levels in liver at multiple time points after TCDD treatment using microRNA arrays along with quantitative RT-PCR. The cumulative results of our experiments indicate that downregulation of mRNA levels by dioxins in adult rodent livers is very unlikely to involve microRNAs.
Manuscript Submitted: Moffat ID, Boutros PC, Celius T, Pohjanvirta R & Okey AB. Micro-RNAs in rodent liver are refractory to dioxin treatment. Toxicological Sciences May, 2007.
Keywords: miRNA expression, Time course, response to xenobiotics, genetic modification, comparative genome hybridization
|
| |
|
| Overall design |
We examined strain differences in miRNA expression independent of TCDD: 19-h vehicle-treated dioxin-resistant H/W AHRH/W/H/W rats (HC19) vs. vehicle- control dioxin-sensitive L-E AHRWT/WT rats (LC19). In the dioxin-sensitive rats we compared miRNA expression levels 3 h (LT3) or 19 h (LT19) post-TCDD treatment vs. LC19. In the dioxin-resistant rats we compared miRNA levels 3 h (HT3), 19 h (HT19), or 96 h (HT96) post-TCDD treatment vs. HC19.
|
| |
|
| Contributor(s) |
Moffat ID, Boutros PC, Celius T, Lindén J, Pohjanvirta R, Okey AB |
| Citation(s) |
17698510 |
| Submission date |
Jul 13, 2007 |
| Last update date |
Mar 19, 2012 |
| Contact name |
Ivy Moffat |
| E-mail(s) |
ivy.moffat@utoronto.ca
|
| Phone |
416-978-2207
|
| Fax |
416-978-6395
|
| Organization name |
University of Toronto
|
| Department |
Pharmacology
|
| Lab |
Dr. Allan B. Okey
|
| Street address |
1 King's College Circle, Medical Science Building Rm.4302
|
| City |
Toronto |
| State/province |
Ontario |
| ZIP/Postal code |
M5S 1A8 |
| Country |
Canada |
| |
|
| Platforms (1) |
| GPL5531 |
Exiqon-Rat/Mouse/Human-540-v8.0 |
|
| Samples (20)
|
| GSM210160 |
L-E rat liver: 19hTCDD vs control replicate1 |
| GSM210161 |
L-E rat liver: control vs 19hTCDD replicate2 |
| GSM210162 |
L-E rat liver: 19hTCDD vs control replicate3 |
| GSM210163 |
L-E rat liver: control vs 19hTCDD replicate4 |
| GSM210164 |
H/W rat liver: 19hTCDD vs control replicate1 |
| GSM210165 |
H/W rat liver: control vs 19hTCDD replicate2 |
| GSM210166 |
H/W rat liver: 19hTCDD vs control replicate3 |
| GSM210167 |
H/W rat liver: control vs 19hTCDD replicate4 |
| GSM210168 |
liver H/W control vs L-E control |
| GSM210169 |
liver L-E control vs H/W control |
| GSM210170 |
L-E rat liver: 3hTCDD vs control replicate1 |
| GSM210171 |
L-E rat liver: control vs 3hTCDD replicate2 |
| GSM210172 |
L-E rat liver: control vs 3hTCDD replicate4 |
| GSM210173 |
L-E rat liver: 3hTCDD vs control replicate3 |
| GSM210174 |
H/W rat liver: control vs 96hTCDD |
| GSM210175 |
H/W rat liver: control vs 3hTCDD |
| GSM210176 |
H/W rat liver: 3hTCDD vs 96hTCDD |
| GSM210177 |
H/W rat liver: 96hTCDD vs control |
| GSM210178 |
H/W rat liver: 96hTCDD vs 3hTCDD |
| GSM210179 |
H/W rat liver: 3hTCDD vs control |
|
| This SubSeries is part of SuperSeries: |
| GSE8474 |
MicroRNAs in adult rodent liver and response to dioxin |
|
| Relations |
| BioProject |
PRJNA105359 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE8470_RAW.tar |
3.6 Mb |
(http)(custom) |
TAR (of GPR) |
| Processed data included within Sample table |
|
|
|
|
 |
Less...
More...