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Regulation of Ag-activated B cells by Nur77/Nr4a1

ABSTRACT: We identify differentially expressed inducible genes in activated B cells harvested from mice lacking expression of the orphan nuclear hormone receptor Nr4a1.

ORGANISM(S): Mus musculus

PROVIDER: GSE146747 | GEO | 2020/03/30

REPOSITORIES: GEO

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Regulation of Ag-activated B cells by Nur77/Nr4a1

Project description:Regulation of Ag-activated B cells by Nur77/Nr4a1

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The orphan nuclear receptor NR4A1 (Nur77, TR3) regulates oxidative and endoplasmic reticulum stress in pancreatic cancer cells

Project description:NR4A1 (Nur77, TR3) is an orphan nuclear receptor that is overexpressed in pancreatic cancer cells and tumors and exhibits pro-oncogenic activity. Knockdown of NR4A1 by RNA interference (siNR4A1) in Panc1 cells and analysis of the proteome resulted in induction of several markers of endoplasmic reticulum (ER) stress including glucose-related protein 78 (GRP78), CCAAT/enhancer-binding protein-homologous protein (CHOP), activating transcription factor-3 (ATF-3) and AFT-6. These effects were accompanied by induction of apoptosis and similar results were observed after treatment of pancreatic cancer cells with the known inactivator of NR4A1, 1,1-bis(3’-indolyl)-1-(p-hydroxyphenyl)methane (DIM-C-pPhOH). Both siNR4A1 (transfected) and DIM-C-pPhOH also induced reactive oxygen species (ROS) and induction of ROS and ER stress by these agents was attenuated after cotreatment with antioxidants. Transfection of Panc1 cells with siNR4A1 follow by analysis of gene expression by arrays identified ROS metabolism genes regulated by NR4A1. Knockdown of one of these genes, thioredoxin domain containing 5 (TXNDC5) also resulted in induction of ROS and ER stress demonstrating that NR4A1 regulates levels of ER stress and ROS in pancreatic cancer cells to facilitate cell proliferation and survival. Inactivation of this receptor by siNR4A1 or DIM-C-pPhOH decreases TXNDC5 resulting in activation of ROS/ER stress and pro-apoptotic pathways and represents a novel pathway for inducing cell death in pancreatic cancer cells. Two groups of samples are included: 1. siControl; 2. siNR4A1 treatment in PAC1 cell. Transfection of Panc1 cells with siNR4A1 follow by analysis of gene expression by arrays identified ROS metabolism genes regulated by NR4A1.

2014-04-30 | E-GEOD-46994 | biostudies-arrayexpress

The orphan nuclear receptor NR4A1 (Nur77, TR3) regulates oxidative and endoplasmic reticulum stress in pancreatic cancer cells

2014-04-30 | GSE46994 | GEO

Genome-wide ChIP-seq analysis of Nr4a1 binding sites in regulatory T (Treg) cells

Project description:We have revealed that Nr4a family nuclear orphan receptors broadly regulate a transcriptional program in Treg cells. In this study, to give an insight into Nr4a-mediated regulation of the transcriptional program in Treg cells, we performed ChIP-seq experiment using anti-Nr4a1 antibodies and a chromatin lysate from Treg cells. Examination of Nr4a1 binding sites in mouse Treg cells.

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RNA analysis of Nr4a1 and Nr4a1-knockout mammary tumor cells from MMTV-PyVT transgenic mice

Project description:MMTV-PyVT Mammary tumors were harvested from PyVT-wild-type (WT), PyVT-Nr4a1 knockout (KO) littermates on a congenic FVB/NJ background,minced and incubated with collagenase type I digestion solution .The digested Mammary tumor cells were collected and maintained in DMEM medium containing 10% FBS for 24 hour.

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Nr4a1 and Nr4a3 upregulate cell cycle genes upregulated in the Nkx6.1 beta-cell proliferation pathway

Project description:Loss of functional beta-cell mass is a hallmark of Type 1 and Type 2 diabetes, and methods for restoring these cells are needed. Nkx6.1 induces beta-cell proliferation, but the pathway by which Nkx6.1 activates beta-cell expansion has not been defined. Here we demonstrate that Nkx6.1 induces expression of the Nr4a1 and Nr4a3 orphan nuclear receptors, and that these factors are both necessary and sufficient for Nkx6.1-mediated Î²-cell proliferation. Overexpression of the Nr4a receptors results in increased expression of key cell cycle inducers E2F1 and cyclin E1. Furthermore, Nr4a receptors induce components of the anaphase-promoting complex, including Ube2c. We set up a microarray using primary rat islets that were left untreated or transduced with adenoviruses overexpressing GFP, Nr4a1 or Nr4a3 for 48 h.

2014-02-18 | E-GEOD-55078 | biostudies-arrayexpress

Nur77-deficiency in bone marrow-derived macrophages modulates inflammatory responses, extracellular matrix homeostasis, phagocytosis and tolerance

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Genome-wide ChIP-seq analysis of Nr4a1 binding sites in regulatory T (Treg) cells

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Gene Expression of Kidney from FHH and Nr4a1 Deficient Rats

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2014-02-06 | E-GEOD-54714 | biostudies-arrayexpress

Nur77-deficiency in bone marrow-derived macrophages modulates inflammatory responses, extracellular matrix homeostasis, phagocytosis and tolerance

Project description:The nuclear orphan receptor Nur77 (NR4A1, TR3, or NGFI-B) has been shown to exhibit an anti-inflammatory function in macrophages. To further elucidate the role of Nur77 in macrophage physiology, we compared the transcriptome of bone marrow-derived macrophages (BMM) from wild-type (WT) and Nur77-knockout (KO) mice both before and after stimulation with IL4 or LPS. Comparison of gene expression in bone marrow-derived macrophages, isolated from 3 wild-type (control) and 3 Nur77-/- mice (case), left untreated or stimulated in triplicate for 8 hours with LPS or IL-4

2016-03-01 | E-GEOD-68167 | biostudies-arrayexpress

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