Hepatic xenobiotic metabolizing enzyme gene expression through the life stages of the mouse
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ABSTRACT:
ORGANISM(S): Mus musculus
SUBMITTER: Hongzu Ren
PROVIDER: E-GEOD-21716 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:We characterized gene expression changes in the developing mouse liver at gestational days (GD) 11.5, 12.5, 13.5, 14.5, 16.5, and 19.5 and in the neonate (postnatal day (PND) 7 and 30) using full-genome microarrays and compared these changes to that in the adult liver. The fetal liver, and to a lesser extent the neonatal liver, exhibited dramatic differences in gene expression compared to adults. Canonical pathway analysis of the fetal liver signature demonstrated increases in functions important in cell replication and DNA fidelity whereas most metabolic pathways of intermediary metabolism were suppressed. Comparison of the dataset to a number of previously published datasets revealed 1) a striking similarity between the fetal liver and that of the pancreas in both mice and humans, 2) a nucleated erythrocyte signature in the fetus and 3) suppression of most xenobiotic metabolism genes throughout development, except a number of transporters associated with expression in hematopoietic cells. Keywords: gene expression/microarray We characterized gene expression changes in the developing mouse liver at gestational days (GD) 19 and in the neonate (postnatal day (PND) 7 and 30) using full-genome microarrays and compared these changes to that in the adult liver. Total RNA was isolated from liver samples and gene expression analyzed using Affymetrix Mouse 430 2.0 GeneChips. Data from 16 samples, with four mice in each of the four age groups, were analyzed.
2010-10-01 | E-GEOD-21224 | biostudies-arrayexpress
Project description:Using full-genome arrays, the expression of all XMEs was examined during fetal (gestation day (GD) 19), neonatal (postnatal day (PND) 7), prepubescent (PND30), middle age (12 mon), and old age (18 and 24 mon) in the C57Bl6/J mouse liver and compared to young adults. Fetal and neonatal life stages had a dramatic effect on XME expression compared to the relatively minor effects of old age. At all life stages except PND30 down-regulated genes outnumbered up-regulated genes. The altered XMEs included those in all of the major metabolic phases including phase I (alcohol and aldehyde dehydrogenase and Cyp genes), phase II (aldo-keto reductase, glutathione-S-transferases, sulfotransferases and UDP-glucuronosyl transferases) and phase III (transporters). We have generated a comprehensive catalog of XME hepatic gene changes through the life stages of the mouse that can be used to predict chemicals and chemical classes different life stages are more sensitive to. Some CEL files used in this study have been submitted through GSE21224. Keywords: gene expression/microarray
2010-10-01 | GSE21716 | GEO
Project description:MicroRNAs (miRNAs) are extensively in diverse biological processes. However, very little is known about the role of miRNAs in mediating thyroid hormones (TH) action. Maintenance of appropriate TH levels is known to be critically important for development, differentiation and maintenance of metabolic balance in mammals. We induced transient hypothyroidism in juvenile mice by short term exposure to methimazole and perchlorate from post natal day (PND) 12 to 15. The expression of miRNAs in the liver was analyzed with the Taqman Low Density Array (containing up to 600 rodent microRNAs). We found the expression of 40 miRNAs was significantly altered in the liver of hypothyroid mice compared to euthyroid controls. Among the miRNAs, miR-1/206/133 exhibited a massive increase in expression (50 – 500 folds). To further explore TH effect on miR-1/206/133, we treated mouse hepatocyte AML 12 cells with 10 nm T3 for 1 hr and 24 hrs. TH treatment induced the down-regulation of miR-1/206/133b at both time points, reaching statistical significance at 24 hrs. To identify the genes targeted by these miRNAs, DNA microarrays were used to examine hepatic mRNA levels in the hypothyroid mouse model alongside controls. We found transcripts from 92 known genes were significantly altered in hypothyroid mice. Web-based target predication softwares (TargetScan and Microcosm) identified 14 of these transcripts as targets of miR-1/106/133. The vast majority of these mRNA targets were significantly down-regulated in hypothyroid mice, corresponding well with the up-regulation of miR-1/206/133 in hypothyroid mouse liver. The results suggest that TH regulation of these genes may occur secondarily via the reduced repression consequent to TH-induced down-regulation of miR-1/206/133. These studies provide novel insight into the role of miRNAs in mediating TH regulation of gene expression. Agilent two-color microarray were used to perform gene expression profile in euthyroid and hypothyroid male mouse livers, 5 biological replicates. TLDA (Taqman microRNA Array) was used to explore the miRNA expression profile in euthyroid and hypothyroid male mouse livers, 4 biological replicates.
2010-08-20 | E-GEOD-21277 | biostudies-arrayexpress
Project description:Thyroid hormones (THs) play a critical role in development and throughout adulthood. THs act through the thyroid receptor (TR), which binds to the TH response element (TRE) to regulate the expression of target genes. Although TH action has been studied for decades, surprisingly few TREs have been well validated and characterized. In this study we used chromatin immunoprecipitation followed by microarray analysis (ChIP-chip) to identify TR-binding sites in juvenile (postnatal day 15) mice liver. Microarray analysis revealed twelve TR-binding sites consistent between all analyzed samples. In silico analysis was carried out to search for moderately conserved classic TRE sequences within these novel binding regions, which led to the identification of six candidate TREs within three binding regions. Luciferase reporter assays confirmed the presence of a TRE in the promoter region of DEAD (Asp-Glu-Ala-Asp) box polypeptide 54 (Ddx54) and thyroid hormone responsive SPOT14 (Thrsp). The TR/retinoid X receptor (RXR) heterodimer and RXR homodiner were shown to bind the promoter region of Ddx54 and drive gene expression in the presence of 9-cis-retinoic acid (9cRA). The promoter region of Thrsp was shown to allow binding of the TR/RXR heterodimer, and both T3 and 9cRA were able to significantly increase luciferase activity. The RXR homodimer was also able to bind the response element in the promoter region of Thrsp and increase luciferase activity. Overall, ChIP-chip analysis revealed a relatively limited number of TR-binding sites in juvenile mouse liver despite previous studies showing that numerous genes can be affected by TH disruption at that developmental stage, suggesting that TH action may also be mediated through other intermediates. Collectively the results provide an important step towards characterizing TR-binding sites and identifying the underlying drivers of TR-gene regulation. Three samples were analyzed (total input and immunoprecipitated for each samples).
2013-11-16 | E-GEOD-52417 | biostudies-arrayexpress
Project description:The heart of a newborn mouse has an exceptional capacity to regenerate from myocardial injury but lose it after a week of life, which has been utilized as a valuable model to explore the cues for heart regeneration. More and more researches indicated that glycoprotein played an important role in cardiac regeneration. Elucidating the glycosylation processes associated with heart regeneration will be beneficial for the molecular mechanism studies of heart regeneration as well as discovery of potential therapeutic strategies for human cardiac diseases. In this work, an integrated glycoproteomic and proteomic analysis were performed to investigate the differences in glycoprotein abundances and site-specific glycosylation occupancy between neonatal day 1 (P1) and day 7 (P7) of mouse hearts. The intact glycoepeptides were enriched and identified in both P1 and P7 hearts. To screen for differentially regulated glycoproteins, we compared the expression levels of intact glycopeptides between P1 and P7 hearts using label free quantification. Eventually, the glycosylation occupancy of site-specific N-glycans were obtained by comparing the alterations of intact glycopeptides with their corresponding protein expression levels obtained from global proteomic analysis. These altered glycosylation patterns among proteins between P1 and P7 mouse hearts have a significant potential to aid our understanding of the regenerative capacity loss in neonatal mouse hearts during the first week, thus leading to novel therapeutic approaches to recover the capacity.
2020-05-26 | PXD017139 | Pride
Project description:Morphogenesis of epithelial tissues relies on the precise developmental control of cell polarity and architecture. In the early Drosophila embryo, the primary epithelium forms during cellularisation, following a tightly controlled genetic programme where specific sets of genes are up-regulated. Some of them, for instance, control membrane invagination between the nuclei anchored at the apical surface of the syncytium. We study the whole genome expression profile aftre DHT treatment in the uteri of gonadectomized mouse. Experiment Overall Design: Ten 10-11 weeks old C57Bl/6 mice were gonadectomized under isoflurane-induced anesthesia and sacrified seven days after GDX. Mice were injected s.c with DHT (0.1mg/mice) or vehicle, at 0.5, 1, 3, 6, 12 or 24 h before sacrifice. Uteri was removed and pooled before total RNA extraction. Samples was hybridized to U74Av2 Genechips (Affymetrix).
2008-10-18 | E-GEOD-6237 | biostudies-arrayexpress
Project description:C57BL/6J mice were from The Jackson Laboratory (Maine, USA) and were housed/caged and fed a standard chow diet until 6 weeks of age whereupon they were placed in one of 4 different dietary regimens for a period of 3 weeks prior to mating. Mice were housed under pathogen-free conditions of 21± 1°C, 40 to 60% humidity, and a 12 h-12 h light/dark cycle. The 4 diet regimens used in this study were: [1] ad lib Standard Chow (Control diet) with ad lib drinking water. [2] Ad lib Standard Chow, with ad lib drinking water containing 0.64 mg/ml (97 mg/Kg body weight) monosodium glutamate (MSG diet). [3] Ad lib Test Diet Purina 5001 with 20% 55-HFCS (5B4K, Purina, USA), and ad lib drinking water (HFCS diet). [4] Ad lib Purina 5001 with 20% 55-HFCS, and ad lib drinking water containing 0.64 mg/ml (97 mg/K body weight) monosodium glutamate (HFCS+MSG diet). See Table 1 for diet composition. Following mating, the 4 groups of dams were maintained on their respective diets throughout the gestation and nursing period. Male offspring used in these experiments were weighed, then weaned onto the same diets and maintained in this regimen until they reached either 16 or 32 weeks of age. Total RNA was prepared from the liver and visceral white adipose tissue (WAT) taken from 16-week-old mice in the 4 different diet groups using Qiagen RNeasy Kit (Qiagen USA) according to the manufacturers instructions and stored at -80 o C.<br>
2009-10-01 | E-MEXP-1909 | biostudies-arrayexpress
Project description:17Ã-Estradiol (E2) is well known to be associated with uterine cancer, endometriosis, and leiomyomas. Although insulin-like growth factor I (IGF-I) has been identified as a mediator of the uterotrophic effect of E2 in several studies, this mechanism is still not well understood. In the present study, identification of the genes modulated by a physiological dose of E2, in the uterus, has been done in ovariectomized mice using Affymetrix microarrays. The E2-induced genomic profile shows that multiple genes belonging to the IGF-I pathway are affected after exposure to E2. Two phases of regulation could be identified. First, from 0 to 6 h, the expression of genes involved in the cell cycle, growth factors, protein tyrosine phosphatases, and MAPK phosphatases is quickly upregulated by E2, while IGF-I receptor and several genes of the MAPK and phosphatidylinositol 3-kinase pathways are downregulated. Later, i.e., from 6 to 24 h, transporters and peptidases/proteases are stimulated, whereas defense-related genes are differentially regulated by E2. Finally, cytoarchitectural genes are modulated later. The present data show that a physiological dose of E2 induces, within 24 h, a series of transcriptional events that promote the uterotrophic effect. Among these, the E2-mediated activation of the IGF-I pathway seems to play a pivotal role in the uterotrophic effect. Furthermore, the protein tyrosine phosphatases and MAPK phosphatases are likely to modulate the estrogenic uterotrophic action by targeting, at different steps, the IGF-I pathway. Experiment Overall Design: Ten 10-11 weeks old C57Bl/6 mice were gonadectomized under isoflurane-induced anesthesia and sacrified seven days after GDX. Mice were injected s.c with E2 (0.05ug/mice) or vehicle, at 0.5, 1, 3, 6, 12 or 24 h before sacrifice. Uteri was removed and pooled before total RNA extraction. Samples was hybridized to U74Av2 Genechips (Affymetrix).
2007-11-14 | E-GEOD-6219 | biostudies-arrayexpress
Project description:The present study was constructed to confirm previous findings that mice on a high fat diet (HFD) treated by subcutaneous injection with exenatide (EXE) at 3µg/kg once daily for 6 weeks develop exocrine pancreatic injury (Rouse et al. 2014). The present study included 12 weeks of EXE exposure at multiple concentrations (3, 10, or 30 Œºg/kg) with multiple endpoints (histopathology evaluations, immunoassay for cytokines, immunostaining of the pancreas, serum chemistries and measurement of trypsin, amylase, and, lipase, and gene expression profiles). Time- and dose-dependent exocrine pancreatic injury was observed in mice associated with EXE exposure in a HFD environment. The time- and dose-dependent morphological changes identified in the pancreas involved acinar cell injury and death (autophagy, apoptosis, necrosis, and atrophy), cell adaptations (hypertrophy and hyperplasia), and cell survival (regeneration) accompanied with varying degrees of inflammatory response leading to secondary injury in pancreatic blood vessels, ducts, and adipose tissues. Gene expression profiles supported the presence of increased signaling for cell survival and altered lipid metabolism. The potential for EXE to cause acute or early chronic pancreatic injury was identified in a HFD environment. In human disease, the influence of pancreatitis risk factors or pre-existing chronic pancreatitis on this injury potential requires further investigation. Male C57BL/6 mice 6 to 8 weeks of age were purchased from Harlan Laboratories (Frederick, MD). Mice were housed individually in an environmentally controlled room (18C-21C, 40%-70% relative humidity) with a twelve-hour light/dark cycle. Mice were initially fed Certified Purina Rodent Chow #5002 (Ralston Purina Co., St. Louis, MO) providing 63% of calories through carbohydrates, 24% from protein, and 13% from fat. Per the experimental design, mice were subsequently placed on a Teklad Custom Research Diet, TD.06415 (Harlan, Frederick, MD), providing 45% of calories through fats (36% saturated, 47% monounsaturated, 17% polyunsaturated), 36% from carbohydrates, and 19% from protein. Water and food were available ad libitum. Thorough out the experiment all mice were weighed weekly and dosing adjusted accordingly for each mouse. A cohort of eighty 6 to 8 week-old male C57BL6 mice were received from Harlan Laboratories. The cohort represented experimental time point of 12 weeks. The cohort was further divided into 4 exenatide (EXE) treatment groups (0, 3, 10, or 30 ug/kg) of 20 mice each. Initially, all mice were placed on HFD for six weeks without additional treatment and were then maintained on HFD for an additional 12 weeks while receiving daily subcutaneous injections of saline or EXE (Creative Peptides, Shirley, NY; 3, 10, or 30 ug/kg). At the 12 week timepoint, twenty-four hours following their final dose, the mice from the treatment cohort were anesthetized with isoflurane and euthanized by exsanguination with collection of blood for serum harvest. The pancreas from 12 mice in each cohort was preserved in 10% formalin for histology processing. The pancreas from 5 mice in each cohort was placed in RNAlater (Life Technologies, Grand Island, NY) for subsequent RNA extraction and the pancreas from 3 mice in each cohort was immediately frozen in liquid nitrogen and then stored at -80C. Pancreas tissue was resected, preserved in RNALater, and stored at -80 C. After thawing, 2.5 mg of each sample were processed using miRNeasy Mini Kits (Cat # 217004) (Qiagen, Valencia, CA). Samples were homogenized in 700 uL of Qiazol Lysis Reagent (Qiagen), for 5 minutes at 50 hz in a TissueLyser LT (Qiagen), and processed using the automated purification of total RNA on a Qiacube (Qiagen), using the 'Purification of total RNA, including small RNAs, from animal tissues & cells (aqueous phase), version 2 (April 2010)' standard protocol, as described in the miRNeasy Mini Handbook (1073008 07/2012) & http://www.qiagen.com/QIAcube/Standard/ProtocolView.aspx?StandardProtocolID=847.Mean yield per 2.5 mg of pancreas tissue was approximately 35 ug, determined by NanoDrop spectrophotometer (Thermo Scientific, Wilmington, DE). Average RIN values were approximately 5.4 +/- 1.4, as assayed by a 2100 Bioanalyzer Instrument (Agilent Technologies, Santa Clara, CA), using an Agilent RNA 6000 Nano Kit (cat # 5067-1511). This RIN mean was consistent with our previous experiences in RNA extraction from murine pancreatic tissue. The isolated RNA was labeled and gene expression analysis performed by Expression Analysis, Inc. (Durham, NC). The 3 samples with the highest RIN from each treatment group were used to probe treatment effect on gene expression. Total RNA samples (100 ng) were converted into cDNA using Ovation WGA FFPE System (NuGEN, Part No. 6200). The second strand cDNA is then purified with Agencourt RNAClean beads and followed by SPIA amplification. Amplified SPIA cDNA product is purified using Agencourt RNAClean beads and quantitated using a NanoDrop ND-8000 spectrophotometer. Target preparation was performed using 4 ug of amplified cDNA and the NuGEN FL-Ovation cDNA Biotin Module V2. Fragmented and biotin-labeled target was hybridized to Affymetrix GeneChip Mouse Genome 430 2.0 microarrays. Raw gene expression data were first analyzed using ArrayTrack bioinformatics tool with robust multichip average algorithm and quantile normalization. Differentially expressed genes were defined by p < 0.05 and fold change > 1.3 in Welch t-test comparing treatment and control groups. Expression data were then imported to Ingenuity Pathway Analysis (IPA) tool for further analyses of pathway, biofunction, and toxicity using general and pancreas-specific knowledge bases.
2014-06-01 | E-GEOD-54774 | biostudies-arrayexpress
Project description:Monuron (1,1-dimethyl-3-(4-chlorophenyl) urea) is a non-selective phenylurea herbicide, widely used in the developing countries, however concerns have been raised about it toxicity and carcinogenicity. Monuron was evaluated by the National Toxicology Program (1988) and shown to be a male rat-specific renal carcinogen; however the mechanism of carcinogenesis is unknown. In this study we have examined the effect of sub-cytotoxic exposure to monuron (250M-BM-5M) at 6h, 24h and 72h on the whole-genome expression profile in a rat proximal renal tubule cell line (NRK-52E). In addition we examined the short term exposure of MON in kidney and liver of exposed rats. We used microarrays to detail the mechanism of toxicity and possibly carcinogenicity of monuron. NRK-52E cells were cultured to confluence on 6-well plates. Cells were then exposed to chlorothalonil dissolved in DMSO (0.1%) at the IC10 concentration at 72h (1.1 M-NM-<M CHL) or DMSO only as control. After 6h, 24h and 72h the medium was removed and RNA was extracted from the cells. Three studies were conducted at each time point. Eight Wistar-derived rats where bred in the Life Science Support Unit at Liverpool John Moores University male rats (190-240g) 7-9 weeks of age were used in this study. Four rats being dosed with MON at 40mg/kg body weight on day 1 and 400mg/kg body weight on days 2 and 3, at 5ml/kg in corn oil. Four control animals were dosed with corn oil at 5ml/kg. Seventy two hours after the last dose all rats were killed by a rising concentration of carbon dioxide, the liver and kidneys quickly removed and immersed in RNAlater.
2015-02-16 | E-GEOD-51163 | biostudies-arrayexpress