Pregnancy-associated changes of peroxisome proliferator-activated receptor delta (PPARD) and cytochrome P450, family 21, subfamily A, polypeptide 2 (CYP21A2) expression in the bovine corpus luteum
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PROVIDER: PRJNA528589 | ENA |
REPOSITORIES: ENA
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Project description:To evaluate functional changes of the corpus luteum (CL) during early pregnancy in cows, gene expression profiles of the CL at the time of maternal recognition were investigated. Microarray analysis, using a 15 K bovine oligo DNA microarray, demonstrated 30 and 266 differentially expressed genes in the CL on days 15 (P15) and 18 (P18) of pregnancy compared with the CL on day 15 (NP15) of non-pregnancy (n=4 for each group, >2-fold change relative to NP15; P<0.05).
2019-09-22 | GSE128706 | GEO
Project description:We investigated gene expression profiles of the corpus luteum (CL) at the time of maternal recognition to evaluate the functional changes of the CL during early pregnancy in cows and help improve reproductive efficiency and avoid defective fetuses. Microarray analyses using a 15 K bovine oligo DNA microarray detected 30 differentially expressed genes and 266 differentially expressed genes (e.g., PPARD and CYP21A2) in the CL on pregnancy days 15 (P15) and 18 (P18), respectively, compared with the CL on day 15 (NP15) of non-pregnancy (n = 4 for each group). PPARD expression was the highest while the CYP21A2 expression was the lowest in P15 and P18 compared with that of NP15. These microarray results were validated by quantitative real-time PCR analysis. The addition of interferon-τ and supernatants derived from homogenized fetal trophoblast increased ISG15 and MX1 expressions in the cultured luteal tissue (P < 0.01), but did not affect PPARD and CYP21A2 expressions. PPARD expression in the luteal tissue was stimulated (P < 0.05) by GW0742, known as a selective PPARD agonist, and PPARD ligands (i.e., arachidonic, linoleic and linolenic acids). In contrast, CYP21A2 mRNA expression was not affected by both agonist and ligands. The concentration of prostaglandin (PG) E2 and PGF2α decreased after GW0742 stimulation and increased after arachidonic acid stimulation (P < 0.05). The addition of GW0742 and arachidonic acid increased progesterone (P4) concentration. Collectively, these findings suggest that high expression levels of PPARD and low expression levels of CYP21A2 in the CL during early pregnancy may support P4 production by bovine luteal cells.
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Project description:Investigation of whole genome gene expression level changes in GW501516 (a Ppard ligand) or Il-4 treated Ppard-overexpressing RAW 264.7 macrophages as compared to vehicle. Alternative activation of adipose tissue resident macrophages inhibits obesity-induced metabolic inflammation. In the current study we profile genes regulated by two M2 inducers, Il-4 or Ppard agonists and find that alternative activation promotes the cell survival program, while inhibiting that of inflammation-related cell death.
2017-06-21 | GSE100237 | GEO
Project description:The role of murine peroxisome proliferator-activated receptor-delta (PPARd) in mammary tumorigenesis was assessed. Microarrays were used to analyse global gene expression to determine changes in MMTV-PPARd transgenic mice versus wild-type mice and the effect of GW501516.
2013-05-31 | GSE34109 | GEO
Project description:The PPAR (Peroxisome proliferator-activated receptor) family of nuclear receptors has three members: PPARg, PPARa and PPARd. Although they share similar structures, their biological functions are distinct. PPARg controls lipid storage and adipogenesis, while PPARd is associated with fat burning. The highly specific synthetic ligand for PPARd, GW501516, is a promising drug candidate for obesity and diabetes. Here we use Affymetrix microarray to analyze gene expression profile in mouse embryo fibroblasts treated with 100 nM GW501516 for 0, 2, 8 and 24 hours. These data may provide new clues into the molecular mechanism by which GW501516 ameliorates obesity and diabetes.
2013-12-31 | GSE20371 | GEO
Project description:The PPAR (Peroxisome proliferator-activated receptor) family of nuclear receptors has three members: PPARg, PPARa and PPARd. Although they share similar structures, their biological functions are distinct. PPARg controls lipid storage and adipogenesis, while PPARd is associated with fat burning. The highly specific synthetic ligand for PPARd, GW501516, is a promising drug candidate for obesity and diabetes. Here we use Affymetrix microarray to analyze gene expression profile in mouse embryo fibroblasts treated with 100 nM GW501516 for 0, 2, 8 and 24 hours. These data may provide new clues into the molecular mechanism by which GW501516 ameliorates obesity and diabetes. Wild type mouse embryonic fibroblasts (MEFs) stably infected with retroviruses MSCVpuro expressing PPARd were plated at 0.5 million per 10 cm dish. After overnight incubation, cells were treated with 100nM GW501516 for 0h, 2h, 8h and 48h. Cells were collected at subconfluent condition. Total RNAs were sequentially purified with Trizol (Invitrogen) and RNeasy kit (Qiagen) and analyzed in triplicate on Mouse Genome 430 2.0 Array (Affymetrix) at NIDDK Microarray Core Facility following standard protocols.
2013-12-31 | E-GEOD-20371 | biostudies-arrayexpress
Project description:The role of murine peroxisome proliferator-activated receptor-delta (PPARd) in mammary tumorigenesis was assessed. Microarrays were used to analyse global gene expression to determine changes in MMTV-PPARd transgenic mice versus wild-type mice and the effect of GW501516. RNA was isolated (RNeasy Mini Kit, Qiagen) from mammary gland tissue of transgenic and wild-type mice maintained on normal rodent chow or 0.005% GW501516
2013-05-31 | E-GEOD-34109 | biostudies-arrayexpress
Project description:Preeclampsia is a multisystem disorder of pregnancy, originating in the placenta. Cytochrome P450 (CYP)-dependent eicosanoids regulate vascular function, inflammation, and angiogenesis, which are mechanistically important in preeclampsia.We performed microarray screening of placenta and decidua (maternal placenta) from 25 preeclamptic women and 23 control subjects. The CYP subfamily 2J polypeptide 2 (CYP2J2) was upregulated in preeclamptic placenta and decidua. Reverse-transcription polymerase chain reaction confirmed the upregulation, and immunohistochemistry localized CYP2J2 in trophoblastic villi and deciduas at 12 weeks and term. The CYP2J2 metabolites, 5,6-epoxyeicosatrienoic acid (EET), 14,15-EET, and the corresponding dihydroxyeicosatrienoic acids, were elevated in preeclamptic women compared with controls in the latter two thirds of pregnancy and after delivery. Stimulating a trophoblast-derived cell line with the preeclampsia-associated cytokine tumor necrosis factor-? enhanced CYP2J2 gene and protein expression. In 2 independent rat models of preeclampsia, reduced uterine-perfusion rat and the transgenic angiotensin II rat, we observed elevated EET, dihydroxyeicosatrienoic acid, and preeclamptic features that were ameliorated by the CYP epoxygenase inhibitor N-(methylsulfonyl)-2-(2-propynyloxy)-benzenehexanamide (MsPPOH). Uterine arterial rings of these rats also dilated in response to MsPPOH. Furthermore, 5,6-EET could be metabolized to a thromboxane analog. In a bioassay, 5,6-EET increased the beating rate of neonatal cardiomyocytes. Blocking thromboxane synthesis reversed that finding and also normalized large-conductance calcium-activated potassium channel activity.Our data implicate CYP2J2 in the pathogenesis of preeclampsia and as a potential candidate for the disturbed uteroplacental remodeling, leading to hypertension and endothelial dysfunction.
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Project description:The cytochrome P450, CYP2C8, metabolizes more than 60 clinically used drugs as well as endogenous substances including retinoic acid and arachidonic acid. However, predictive factors for interindividual variability in the efficacy and toxicity of CYP2C8 drug substrates are essentially lacking. Recently we demonstrated that peroxisome proliferator-activated receptor alpha (PPAR?), a nuclear receptor primarily involved in control of lipid and energy homeostasis directly regulates the transcription of CYP3A4. Here we investigated the potential regulation of CYP2C8 by PPAR?. Two linked intronic SNPs in PPAR? (rs4253728, rs4823613) previously associated with hepatic CYP3A4 status showed significant association with CYP2C8 protein level in human liver samples (N = 150). Furthermore, siRNA-mediated knock-down of PPAR? in HepaRG human hepatocyte cells resulted in up to ?60 and ?50% downregulation of CYP2C8 mRNA and activity, while treatment with the PPAR? agonist WY14,643 lead to an induction by >150 and >100%, respectively. Using chromatin immunoprecipitation scanning assay we identified a specific upstream gene region that is occupied in vivo by PPAR?. Electromobility shift assay demonstrated direct binding of PPAR? to a DR-1 motif located at positions -2762/-2775 bp upstream of the CYP2C8 transcription start site. We further validated the functional activity of this element using luciferase reporter gene assays in HuH7 cells. Moreover, based on our previous studies we demonstrated that WNT/?-catenin acts as a functional inhibitor of PPAR?-mediated inducibility of CYP2C8 expression. In conclusion, our data suggest direct involvement of PPAR? in both constitutive and inducible regulation of CYP2C8 expression in human liver, which is further modulated by WNT/?-catenin pathway. PPARA gene polymorphism could have a modest influence on CYP2C8 phenotype.
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