Transcriptional profiling of hepatic stellate cells transfected with COUP-TFII
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Luca Beltrame
PROVIDER: E-MTAB-1795 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:Recent studies demonstrated that metabolic disturbance, such as augmented glycolysis, contributes to fibrosis. The molecular regulation of this metabolic perturbation in fibrosis, however, has been elusive. COUP-TFII (also known as NR2F2) is an important regulator of glucose and lipid metabolism. Its contribution to organ fibrosis is undefined. Here, we found increased COUP-TFII expression in myofibroblasts in human fibrotic kidneys, lungs, kidney organoids, and mouse kidneys after injury. Genetic ablation of COUP-TFII in mice resulted in attenuation of injury-induced kidney fibrosis. A non-biased proteomic study revealed the suppression of fatty acid oxidation and the enhancement of glycolysis pathways in COUP-TFII overexpressing fibroblasts. Overexpression of COUP-TFII in fibroblasts induced augmented glycolysis and production of alpha smooth muscle actin (αSMA) and collagen1. Knockout of COUP-TFII decreased glycolysis and collagen1 levels in fibroblasts. Chip-qPCR revealed the binding of COUP-TFII on the promoter of PGC1α. Overexpression of COUP-TFII reduced the cellular level of PGC1α. Targeting COUP-TFII serves as a novel treatment approach for mitigating fibrosis in chronic kidney disease and potentially fibrosis in other organs.
2021-04-27 | PXD024035 | Pride
Project description:Pancreatic β-cells have the key homeostatic function of releasing insulin to keep blood glucose in the normal range. It is not fully understood how β-cell mass is determined. Ablation of a nuclear receptor, chicken ovalbumin upstream promoter transcription factor II (COUP-TFII), in mouse pancreatic β-cells results in glucose intolerance and 50% fewer β-cells during the postnatal period. By testing islets isolated from these mice and cultured β-cells with loss and gain of COUP-TFII function, we found that COUP-TFII induces β-catenin thus upregulating target genes like cyclin D1. Beta-cell expansion triggered by glucagon-like peptide 1 (GLP-1) is known to be mediated by β-catenin controlling cyclin D1. We show that in the absence of COUP-TFII, exendin-4, an agonist of the GLP-1 receptor, does not fully induce cyclin D1 expression, while overexpression of β-catenin induces cyclin D1. A marked decrease in cyclin D1 expression is detected in islets isolated from transgenic mice lacking both GLP-1 receptor and gastric inhibitory peptide receptor. COUP-TFII is therefore required for GLP-1 activation of the β-catenin-dependent pathway in pancreatic β-cells to increase β-cell number. To understand the molecular mechanisms by which COUP-TFII controls β-cell mass, we determined the RNA profile of COUP-TFII knockdown β-cells using Affymetrix oligonucleotide microarrays. Computational analysis identified clusters of genes shared by different gene regulatory Networks that are up or down regulated namely genes involved in Wnt/β-catenin signaling, insulin signaling and lipid/carbohydrate metabolism. We determined the RNA profile of COUP-TFII knockdown β-cells (832/13 INS-1 cells transfected with COUP-TFII specific siRNA) with respect to control cells (832/13 INS-1 cells transfected with scrambled siRNA) using Affymetrix expression analysis technical manual 701025Rev.5 (Affymetrix, Santa Clara, California, USA). Briefly, 1 mg of total cellular mRNA was reverse transcribed into cDNA (SuperScript Choice System Invitrogen, Carlsbad, CA) using oligo-dT primers and a T7 RNA polymerase promoter site. The cDNA was in vitro transcribed and biotin-labeled for microarray analysis using the Affymetrix IVT labeling kit. The concentration of labelled cRNA was measured using a NanoDrop ND-1000 spectrophotometer. Labeled cRNA was fragmented in a fragmentation buffer for 35 min at 94°C. The quality of labeled and fragmented cRNA was analyzed using the Agilent bioanalyzer 2100 (Van Lommel et al, 2006). Fragmented cRNA was hybridized to the rat 230 2.0 array (Affymetrix) during 16h at 45°C. Arrays were washed and stained in a fluidics station (Affymetrix) and scanned using the Affymetrix 3000 GeneScanner.
2011-10-06 | E-GEOD-30526 | biostudies-arrayexpress
Project description:COUP-TFII plays a critical role in angiogenesis during development. It has also been shown to suppress Notch signaling pathway to confer vein identity. However, the downstream targets and the mechanism mediate COUP-TFII function to regulate these processes remain elusive. To identify the downstream targets and the mechanism by which COUP-TFII regulates agiogenesis and vein specification, we knocked down COUP-TFII in HUVEC cells using COUP-TFII specific siRNA and used microarray analysis to identify downstream targets. Interestingly, we found the expression of many genes in the cell cycle pathway and Notch signaling pathway are significantly altered in the COUP-TFII depleted cells. HUVEC Cells were transfected with siRNA (Control or COUP-TFII siRNA) duplexes (50 nM) and total RNA was isolated 48 hours later.
2011-10-27 | E-GEOD-33301 | biostudies-arrayexpress
Project description:COUP-TFII, a member of the nuclear receptor superfamily plays a critical role in angiogenesis and organogenesis during embryonic development. Our results indicate that COUP-TFII expression is profoundly upregulated in prostate cancer patients and might serves as biomarker for recurrence prediction. Thus we conduct transcriptome comparison of control and COUP-TFII depleted PC3 cells to gain genomic insights on the biological processes that COUP-TFII is involved in prostate cancer cells. Ingenuity Pathway Analysis (IPA) shows that the most prominent altered pathways in the COUP-TFII depleted cells are related to cell growth; cell cycle progression and DNA damage response. Indeed many growth related genes including E2F1, p21, CDC25A, Cyclin A and Cyclin B are changed in COUP-TFII knockdown cells, suggesting that COUP-TFII might be an important regulator for prostate cancer cell growth. Further functional assays from cells and mice genetic studies confirm the hypothesis that COUP-TFII serve as the major regulator to control prostrate cancer growth. Together, results provide insight into the role of COUP-TFII in prostate tumorigenesis. PC3 Cells were transfected with siRNA (Control or COUP-TFII siRNA) duplexes (40 nM) and total RNA was isolated 48 hours later.
2011-10-24 | E-GEOD-33182 | biostudies-arrayexpress
Project description:Although the function of COUP-TFII in uterine decidualization has been described in mice, its role in the human uterus remains unknown.To interrogate the role of COUP-TFII in human endometrial function, we utilized a siRNA-mediated loss of function approach in primary human endometrial stromal cells. Primary human endometrial stromal cells (HESCs), coup-TFII siRNA group and control group Two group comparison
2014-01-07 | E-GEOD-47052 | biostudies-arrayexpress
Project description:The orphan nuclear receptor COUP-TFII is expressed at a low level in adult tissues, but its expression is increased and shown to promote progression of multiple diseases including prostate cancer, heart failure and muscular dystrophy. Suppression of COUP-TFII slows disease progression, making it an intriguing therapeutic target. Here, we identified a potent and specific COUP-TFII inhibitor through high-throughput screening. The inhibitor specifically suppressed COUP-TFII activity to regulate its target genes.
2020-05-12 | GSE142475 | GEO
Project description:Elevated COUP-TFII levels are found in Parkinson’s disease. COUP-TFII overexpression in mouse dopaminergic neurons caused neurodegeneration. The goal of this study is to identify molecular mechanisms of COUP-TFII-mediated cell death through RNAseq.
2020-05-29 | GSE132874 | GEO
Project description:COUP-TFII, a member of the nuclear receptor superfamily plays a critical role in angiogenesis and organogenesis during embryonic development. Our results indicate that COUP-TFII expression is profoundly upregulated in prostate cancer patients and might serves as biomarker for recurrence prediction. Thus we conduct transcriptome comparison of control and COUP-TFII depleted PC3 cells to gain genomic insights on the biological processes that COUP-TFII is involved in prostate cancer cells. Ingenuity Pathway Analysis (IPA) shows that the most prominent altered pathways in the COUP-TFII depleted cells are related to cell growth; cell cycle progression and DNA damage response. Indeed many growth related genes including E2F1, p21, CDC25A, Cyclin A and Cyclin B are changed in COUP-TFII knockdown cells, suggesting that COUP-TFII might be an important regulator for prostate cancer cell growth. Further functional assays from cells and mice genetic studies confirm the hypothesis that COUP-TFII serve as the major regulator to control prostrate cancer growth. Together, results provide insight into the role of COUP-TFII in prostate tumorigenesis.
2011-10-25 | GSE33182 | GEO
Project description:Increased COUP-TFII levels are found in human dilated cardiomyopathy as well as in mouse models that develop cardiomyopathy. COUP-TFII overexpression in adult mouse hearts caused ventricular dilation and compromised cardiac functions. To gain insights on COUP-TFII’s effect in hearts, we identified the molecular profile of COUP-TFII overexpressing hearts through microarray analysis. The result may shred light on molecular mechanisms that mediate development of dilated cardiomyopathy.
2015-07-24 | GSE63759 | GEO
Project description:COUP-TFII plays a critical role in angiogenesis during development. It has also been shown to suppress Notch signaling pathway to confer vein identity. However, the downstream targets and the mechanism mediate COUP-TFII function to regulate these processes remain elusive. To identify the downstream targets and the mechanism by which COUP-TFII regulates agiogenesis and vein specification, we knocked down COUP-TFII in HUVEC cells using COUP-TFII specific siRNA and used microarray analysis to identify downstream targets. Interestingly, we found the expression of many genes in the cell cycle pathway and Notch signaling pathway are significantly altered in the COUP-TFII depleted cells.
2011-10-28 | GSE33301 | GEO