1,348 results match your criteria nr4a1


Effect of repeated seizures on spatial exploration and immediate early gene expression in the hippocampus and dentate gyrus.

IBRO Neurosci Rep 2022 Jun 31;12:73-80. Epub 2021 Dec 31.

Department of Psychology, Trent University, Peterborough, ON K9J 7B8, Canada.

Immediate early genes (IEGs) are coordinately activated in response to neuronal activity and can cause activation of secondary response genes that modulate synaptic plasticity and mediate long-lasting changes in behaviour. Excessive neuronal stimulation induced by epileptic seizures induce rapid and dramatic changes in IEG expression. Although the impact of acute seizure activity on IEG expression has been well studied, less is known about the long-term effects of chronic seizures on IEG induction during seizure free periods where behavioural and cognitive impairments are frequently observed in people with epilepsy and in animal models of epilepsy. Read More

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Cytosporone B (Csn-B), an NR4A1 agonist, attenuates acute cardiac allograft rejection by inducing differential apoptosis of CD4+T cells.

Int Immunopharmacol 2022 Jan 10;104:108521. Epub 2022 Jan 10.

Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address:

CD4+T cell-mediated acute rejection remains a major factor that affects the early survival of transplanted organs post-transplantation. Here, we reveal that nuclear receptor subfamily 4 Group A member 1 (Nr4A1) was upregulated during cardiac allograft rejection and that the increased Nr4A1 was primarily localized in intragraft-infiltrating CD4+T cells. Nr4A1 acts as a transcription factor with an important role in CD4+T cell apoptosis, differentiation and T cell dysfunction, which indicates that Nr4A1 may play a critical role in transplant rejection. Read More

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January 2022

Evaluation of animal model congruence to human depression based on large-scale gene expression patterns of the CNS.

Authors:
Stephen C Gammie

Sci Rep 2022 Jan 7;12(1):108. Epub 2022 Jan 7.

Department of Integrative Biology, University of Wisconsin-Madison, Madison, USA.

Depression is a complex mental health disorder that is difficult to study. A wide range of animal models exist and for many of these data on large-scale gene expression patterns in the CNS are available. The goal of this study was to evaluate how well animal models match human depression by evaluating congruence and discordance of large-scale gene expression patterns in the CNS between almost 300 animal models and a portrait of human depression created from male and female datasets. Read More

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January 2022

Colorectal Cancer-Associated Immune Exhaustion Involves T and B Lymphocytes and Conventional NK Cells and Correlates With a Shorter Overall Survival.

Front Immunol 2021 16;12:778329. Epub 2021 Dec 16.

Department of Medicine and Sciences of Aging, "G. d'Annunzio" University" of Chieti-Pescara, Chieti, Italy.

Colorectal cancer (CRC) is one of the most common cancer worldwide, with a growing impact on public health and clinical management. Immunotherapy has shown promise in the treatment of advanced cancers, but needs to be improved for CRC, since only a limited fraction of patients is eligible for treatment, and most of them develop resistance due to progressive immune exhaustion. Here, we identify the transcriptional, molecular, and cellular traits of the immune exhaustion associated with CRC and determine their relationships with the patient's clinic-pathological profile. Read More

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December 2021

Nur77 ameliorates age-related renal tubulointerstitial fibrosis by suppressing the TGF-β/Smads signaling pathway.

FASEB J 2022 02;36(2):e22124

Department of Gerontology and Geriatrics, Shengjing Hospital of China Medical University, Shenyang, China.

Nerve growth factor-induced gene B (Nur77) has been shown to ameliorate several biological processes in chronic diseases, including inflammatory response, cellular proliferation, and metabolism. Chronic kidney disease (CKD) is characterized by tubulointerstitial fibrosis for which no targeted therapies are available as yet. In this study, we performed in vivo and in vitro experiments to demonstrate that Nur77 targets fibrosis signals and attenuates renal tubulointerstitial fibrosis during the aging process. Read More

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February 2022

Changes in Transcriptomic Profiles in Different Reproductive Periods in Yaks.

Biology (Basel) 2021 Nov 25;10(12). Epub 2021 Nov 25.

Key Laboratory of Yak Breeding Engineering of Gansu Province, Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences, Lanzhou 730050, China.

Yak reproductive characteristics have received extensive attention, though the molecular regulation mechanism of its ovarian activity remains to be explored. Therefore, this study initially conducted a comparative analysis of yak ovarian activities in anestrus, estrus, and pregnancy regarding their morphology and histology, followed by implementing RNA sequencing (RNA-seq) technology to detect the overall gene expression and biological mechanism in different reproductive stages. H&E staining showed that there were more growing follicles and mature follicles in ovarian tissue sections during estrus than ovarian tissues during non-estrus. Read More

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November 2021

Bladder Exposure to Activates Host Pathways Necessary for Recurrent UTI.

Front Cell Infect Microbiol 2021 6;11:788229. Epub 2021 Dec 6.

Department of Pediatrics, Division of Infectious Diseases, Washington University in St. Louis School of Medicine, St. Louis, MO, United States.

Recurrent urinary tract infections (rUTI) are a costly clinical problem affecting millions of women worldwide each year. The majority of rUTI cases are caused by uropathogenic (UPEC). Data from humans and mouse models indicate that some instances of rUTI are caused by UPEC emerging from latent reservoirs in the bladder. Read More

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December 2021

NR4A1 suppresses pyroptosis by transcriptionally inhibiting NLRP3 and IL-1β and co-localizing with NLRP3 in trans-Golgi to alleviate pathogenic bacteria-induced colitis.

Clin Transl Med 2021 12;11(12):e639

Department of Animal Nutrition and Feed Science, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan, 430070, P. R. China.

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December 2021

Directly recruited GATA6 + peritoneal cavity macrophages contribute to the repair of intestinal serosal injury.

Nat Commun 2021 12 15;12(1):7294. Epub 2021 Dec 15.

Department of Transplantation and Pediatric Surgery, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan.

Recruitment of bone marrow derived monocytes via bloodstream and their subsequent conversion to CX3CR1 macrophages in response to intestinal injury is dependent on CCR2, Nr4a1, and the microbiome. This process is critical for proper tissue repair; however, GATA6 peritoneal cavity macrophages might represent an alternative, more readily available source of mature and functional myeloid cells at the damaged intestinal locations. Here we show, using spinning-disk confocal microscopy, that large F4/80GATA6 peritoneal cavity macrophages promptly accumulate at damaged intestinal sites upon intestinal thermal injury and upon dextran sodium sulfate induced colitis in mice via a direct route from the peritoneal cavity. Read More

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December 2021

Inflammatory Monocyte Counts Determine Venous Blood Clot Formation and Resolution.

Arterioscler Thromb Vasc Biol 2021 12 16:ATVBAHA121317176. Epub 2021 Dec 16.

Department of Dermatology, Westfälische Wilhelms-University Münster, Germany

Background: Monocytes are thought to be involved in venous thrombosis but the role of individual monocyte subpopulations on thrombus formation, clot inflammation, and degradation is an important unresolved issue. We investigate the role of inflammatory Ly6C monocytes in deep vein thrombosis and their potential therapeutic impact.

Methods: Frequencies and compositions of blood monocytes were analyzed by flow cytometry in CCR2 (C-C chemokine receptor type 2) and wild-type mice of different ages and after treatment with the NR4A1 (nuclear receptor group 4 family A member 1, Nur77) agonist CnsB (cytosporone B). Read More

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December 2021

Flavonoids kaempferol and quercetin are nuclear receptor 4A1 (NR4A1, Nur77) ligands and inhibit rhabdomyosarcoma cell and tumor growth.

J Exp Clin Cancer Res 2021 Dec 14;40(1):392. Epub 2021 Dec 14.

Department of Veterinary Physiology and Pharmacology, Texas A&M University, 4466 TAMU, College Station, TX, 77843-4466, USA.

Background: Flavonoids exhibit both chemopreventive and chemotherapeutic activity for multiple tumor types, however, their mechanisms of action are not well defined. Based on some of their functional and gene modifying activities as anticancer agents, we hypothesized that kaempferol and quercetin were nuclear receptor 4A1 (NR4A1, Nur77) ligands and confirmed that both compounds directly bound NR4A1 with K values of 3.1 and 0. Read More

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December 2021

Effects of Training Status and Exercise Mode on Global Gene Expression in Skeletal Muscle.

Int J Mol Sci 2021 Nov 22;22(22). Epub 2021 Nov 22.

Division of Sports and Rehabilitation Medicine, Department of Internal Medicine II, University of Ulm, 89075 Ulm, Germany.

The aim of this study was to investigate differences in skeletal muscle gene expression of highly trained endurance and strength athletes in comparison to untrained individuals at rest and in response to either an acute bout of endurance or strength exercise. Endurance (ET, = 8, VOmax 67 ± 9 mL/kg/min) and strength athletes (ST, = 8, 5.8 ± 3. Read More

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November 2021

Differential Gene Expression in Bladder Tumors from Workers Occupationally Exposed to Arylamines.

Biomed Res Int 2021 8;2021:2624433. Epub 2021 Nov 8.

Epigenetics & Stem Cell Biology Laboratory, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, NC, USA.

Occupational exposure to the arylamines benzidine and -naphthylamine increase bladder cancer risk up to 100-fold, making them some of the most powerful human carcinogens. We hypothesize that tumors arising in people with occupational exposures have different patterns of gene expression than histologically similar tumors from people without such exposures. In a case-case study, we compare gene expression in 22 formalin-fixed paraffin-embedded (FFPE) bladder tumors from men with high-level occupational exposure to arylamines to that in 26 FFPE bladder tumors from men without such exposure. Read More

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November 2021

NR4A1 Affects Endometrial Receptivity by Participating in Mesenchymal-Epithelial Transition of Endometrial Stromal Cells.

Reprod Sci 2022 01 12;29(1):133-142. Epub 2021 Nov 12.

Department of Reproductive Medical Centre, The First People's Hospital of Yunnan Province, No. 157, Jinbi Road, Kunming City, 650000, Yunnan Province, China.

Decidualization is a substantive differentiation process experienced by endometrium to prepare for pregnancy. During this process, the endometrial stromal cells are transformed to endometrial epithelial cells. The receptivity of endometrium is necessary for the decidualization and successful implantation of endometrium, while the main hormones coordinating this process are estrogen and progesterone (P). Read More

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January 2022

Circ_0057583 facilitates brain microvascular endothelial cell injury through modulating miR-204-5p/NR4A1 axis.

Metab Brain Dis 2021 Nov 12. Epub 2021 Nov 12.

Department of Medicine Laboratory, Fuwai Central China Cardiovascular Hospital, Zhengzhou, 450003, China.

Lipopolysaccharide (LPS) can induce vascular endothelial injury. Circular RNAs (circRNAs) have been verified to regulate different cellular processes in various diseases. This study intended to explore the potential role and mechanism of circ_0057583 in brain microvascular endothelial cell injury. Read More

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November 2021

[Analysis of hub genes and molecular mechanisms in non-alcoholic steatohepatitis based on the gene expression omnibus database].

Authors:
L Y Li J X Wu

Zhonghua Yi Xue Za Zhi 2021 Nov;101(40):3317-3322

Beijing Tongren Hospital, Capital Medical University, Beijing 100730, China.

To explore the hub genes and mechanisms in the pathological process of non-alcoholic steatohepatitis (NASH) by bioinformatics methods. Microarray datasets GSE89632 were downloaded from the Gene Expression Omnibus (GEO) database, which including 20 simple non-alcoholic fatty liver disease patients, 19 NASH patients and 24 healthy control individuals. The differentially expressed genes (DEGs) in patients with simple non-alcoholic fatty liver disease and NASH were compared with healthy control individuals respectively, and the intersection of the two groups of DEGs was taken. Read More

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November 2021

Transcription factors specificity protein and nuclear receptor 4A1 in pancreatic cancer.

World J Gastroenterol 2021 Oct;27(38):6387-6398

Department of Medical Oncology, Houston Methodist Hospital Cancer Center, Houston, TX 77030, United States.

Specificity protein (Sp) transcription factors (TFs) Sp1, Sp3 and Sp4, and the orphan nuclear receptor 4A1 (NR4A1) are highly expressed in pancreatic tumors and Sp1 is a negative prognostic factor for pancreatic cancer patient survival. Results of knockdown and overexpression of Sp1, Sp3 and Sp4 in pancreatic and other cancer lines show that these TFs are individually pro-oncogenic factors and loss of one Sp TF is not compensated by other members. NR4A1 is also a pro-oncogenic factor and both NR4A1 and Sp TFs exhibit similar functions in pancreatic cancer cells and regulate cell growth, survival, migration and invasion. Read More

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October 2021

Seasonal regulation of singing-driven gene expression associated with song plasticity in the canary, an open-ended vocal learner.

Mol Brain 2021 10 29;14(1):160. Epub 2021 Oct 29.

Graduate School of Life Science, Hokkaido University, Sapporo, Hokkaido, Japan.

Songbirds are one of the few animal taxa that possess vocal learning abilities. Different species of songbirds exhibit species-specific learning programs during song acquisition. Songbirds with open-ended vocal learning capacity, such as the canary, modify their songs during adulthood. Read More

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October 2021

Effects of gonadotropin inducible ovarian transcription factor 1 in the paraventricular nucleus on fluid intake after dehydration of ovariectomized female rats.

Exp Physiol 2021 Dec 12;106(12):2391-2399. Epub 2021 Nov 12.

Department of Physiology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Sao Paulo, Brazil.

New Findings: What is the central question of this study? Giot1, the gene for gonadotropin inducible ovarian transcription factor 1 (GIOT1), is upregulated in osmotically challenged rats: does Giot1 gene expression in the paraventricular nucleus have a role in controlling fluid intake following dehydration and what is the role of ovarian hormones in the modulation of GIOT1 actions? What is the main finding and its importance? GIOT1 acts to regulate water and salt intake as well as hormone secretion after dehydration. The identification of genes that participate in the hormone and behavioural responses involved with hydromineral homeostasis is essential for future exploration of novel drug targets for the treatment of metabolic disease.

Abstract: In order to maintain body fluid balance after dehydration, hypothalamic neurons of the paraventricular nucleus (PVN) are activated to promote secretion of vasopressin (AVP) and oxytocin (OXT) from the neurohypophysis, and to modulate the behavioural allostatic responses of thirst and salt appetite. Read More

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December 2021

Nuclear receptor 4A1 (NR4A1) antagonists target paraspeckle component 1 (PSPC1) in cancer cells.

Mol Carcinog 2022 01 26;61(1):73-84. Epub 2021 Oct 26.

Department of Veterinary Physiology and Pharmacology, Texas A&M University, College Station, Texas, USA.

Paraspeckles compound 1 (PSPC1) is a multifunctional protein that plays an important role in cancer cells, where PSPC1 is a master regulator of pro-oncogenic responses that includes activation of TGFβ (TGFβ1), TGFβ-dependent EMT, and metastasis. The pro-oncogenic activities of PSPC1 closely resembled those observed for the orphan nuclear receptor 4A1 (NR4A1, Nur77) and knockdown of NR4A1 decreased expression of PSPC1 in MDA-MB-231 breast, H1299 lung, and SNU449 liver cancer cells. Similar results were observed in these same cell lines after treatment with bisindole-derived (CDIMs) NR4A1 antagonists. Read More

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January 2022

Venlafaxine-induced adrenergic signaling stimulates Leydig cells steroidogenesis via Nur77 overexpression: A possible role of EGF.

Life Sci 2022 Jan 21;289:120069. Epub 2021 Oct 21.

São Paulo State University (Unesp), School of Dentistry, Department of Morphology, Genetics, Orthodontics and Pediatric Dentistry, Araraquara, Brazil. Electronic address:

Venlafaxine, a norepinephrine and serotonin reuptake inhibitor, impairs rat sperm parameters, spermatogenesis and causes high intratesticular estrogen and testosterone levels, indicating that Leydig cells (LCs) may be a venlafaxine target. We evaluated the effect of venlafaxine treatment on rat LCs, focusing on adrenergic signaling, EGF immunoexpression and steroidogenesis. Germ cells mitotic/meiotic activity and UCHL1 levels were also evaluated in the seminiferous epithelium. Read More

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January 2022

SPDEF suppresses head and neck squamous cell carcinoma progression by transcriptionally activating NR4A1.

Int J Oral Sci 2021 10 20;13(1):33. Epub 2021 Oct 20.

Hospital of Stomatology, Sun Yat-sen University, Guangzhou, China.

SAM pointed domain containing E26 transformation-specific transcription factor (SPDEF) plays dual roles in the initiation and development of human malignancies. However, the biological role of SPDEF in head and neck squamous cell carcinoma (HNSCC) remains unclear. In this study, the expression level of SPDEF and its correlation with the clinical parameters of patients with HNSCC were determined using TCGA-HNSC, GSE65858, and our own clinical cohorts. Read More

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October 2021

Gene expression in the dorsolateral and ventromedial prefrontal cortices implicates immune-related gene networks in PTSD.

Neurobiol Stress 2021 Nov 20;15:100398. Epub 2021 Sep 20.

National Center for PTSD, Behavioral Sciences Division, VA Boston Healthcare System, Boston, MA, 02130, USA.

Studies evaluating neuroimaging, genetically predicted gene expression, and pre-clinical genetic models of PTSD, have identified PTSD-related abnormalities in the prefrontal cortex (PFC) of the brain, particularly in dorsolateral and ventromedial PFC (dlPFC and vmPFC). In this study, RNA sequencing was used to examine gene expression in the dlPFC and vmPFC using tissue from the VA National PTSD Brain Bank in donors with histories of PTSD with or without depression (dlPFC n = 38, vmPFC n = 35), depression cases without PTSD (n = 32), and psychopathology-free controls (dlPFC n = 24, vmPFC n = 20). Analyses compared PTSD cases to controls. Read More

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November 2021

Phase separation of Nur77 mediates celastrol-induced mitophagy by promoting the liquidity of p62/SQSTM1 condensates.

Nat Commun 2021 10 13;12(1):5989. Epub 2021 Oct 13.

School of Pharmaceutical Sciences, Fujian Provincial Key Laboratory of Innovative Drug Target Research, Xiamen University, Xiamen, 361102, China.

Liquid-liquid phase separation promotes the formation of membraneless condensates that mediate diverse cellular functions, including autophagy of misfolded proteins. However, how phase separation participates in autophagy of dysfunctional mitochondria (mitophagy) remains obscure. We previously discovered that nuclear receptor Nur77 (also called TR3, NGFI-B, or NR4A1) translocates from the nucleus to mitochondria to mediate celastrol-induced mitophagy through interaction with p62/SQSTM1. Read More

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October 2021

NR4A1 regulates expression of immediate early genes, suppressing replication stress in cancer.

Mol Cell 2021 10;81(19):4041-4058.e15

Massachusetts General Hospital Cancer Center, Boston, MA, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA; Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA. Electronic address:

Deregulation of oncogenic signals in cancer triggers replication stress. Immediate early genes (IEGs) are rapidly and transiently expressed following stressful signals, contributing to an integrated response. Here, we find that the orphan nuclear receptor NR4A1 localizes across the gene body and 3' UTR of IEGs, where it inhibits transcriptional elongation by RNA Pol II, generating R-loops and accessible chromatin domains. Read More

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October 2021

Dual imaging of dendritic spines and mitochondria reveals hotspots of plasticity and metabolic adaptation to stress.

Neurobiol Stress 2021 Nov 21;15:100402. Epub 2021 Sep 21.

Institut de Génomique Fonctionnelle, Université de Montpellier, INSERM, CNRS, 34090, Montpellier, France.

Metabolic adaptation is a critical feature of synaptic plasticity. Indeed, synaptic plasticity requires the utilization and resupply of metabolites, in particular when the turnover is high and fast such as in stress conditions. What accounts for the localized energy burden of the post-synaptic compartment to the build up of chronic stress is currently not understood. Read More

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November 2021

Unbiased identification of novel transcription factors in striatal compartmentation and striosome maturation.

Elife 2021 10 5;10. Epub 2021 Oct 5.

Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, United States.

Many diseases are linked to dysregulation of the striatum. Striatal function depends on neuronal compartmentation into striosomes and matrix. Striatal projection neurons are GABAergic medium spiny neurons (MSNs), subtyped by selective expression of receptors, neuropeptides, and other gene families. Read More

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October 2021

The multifaceted regulation of mitophagy by endogenous metabolites.

Autophagy 2021 Sep 29:1-24. Epub 2021 Sep 29.

State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China.

Owing to the dominant functions of mitochondria in multiple cellular metabolisms and distinct types of regulated cell death, maintaining a functional mitochondrial network is fundamental for the cellular homeostasis and body fitness in response to physiological adaptations and stressed conditions. The process of mitophagy, in which the dysfunctional or superfluous mitochondria are selectively engulfed by autophagosome and subsequently degraded in lysosome, has been well formulated as one of the major mechanisms for mitochondrial quality control. To date, the PINK1-PRKN-dependent and receptors (including proteins and lipids)-dependent pathways have been characterized to determine the mitophagy in mammalian cells. Read More

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September 2021

Cytokine exposure mediates transcriptional activation of the orphan nuclear receptor Nur77 in hematopoietic cells.

J Biol Chem 2021 11 24;297(5):101240. Epub 2021 Sep 24.

Department of Internal Medicine, Washington University, St Louis, Missouri, USA. Electronic address:

The orphan nuclear receptor Nur77 is an immediate-early response gene that based on tissue and cell context is implicated in a plethora of cellular processes, including proliferation, differentiation, apoptosis, metabolism, and inflammation. Nur77 has a ligand-binding pocket that is obstructed by hydrophobic side groups. Naturally occurring, cell-endogenous ligands have not been identified, and Nur77 transcriptional activity is thought to be regulated through posttranslational modification and modulation of protein levels. Read More

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November 2021

Deletion of pleiotrophin impairs glucose tolerance and liver metabolism in pregnant mice: Moonlighting role of glycerol kinase.

FASEB J 2021 10;35(10):e21911

Department of Chemistry and Biochemistry, Facultad de Farmacia, Universidad San Pablo-CEU, CEU Universities, Alcorcón, Spain.

Pleiotrophin is a pleiotropic cytokine that has been demonstrated to have a critical role in regulating energy metabolism, lipid turnover and plasticity of adipose tissue. Here, we hypothesize that this cytokine can be involved in regulatory processes of glucose and lipid homeostasis in the liver during pregnancy. Using 18-days pregnant Ptn-deficient mice, we evaluated the biochemical profile (circulating variables), tissue mRNA expression (qPCR) and protein levels of key enzymes and transcription factors involved in main metabolic pathways. Read More

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October 2021