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https://www.readbyqxmd.com/read/29047330/deletion-of-the-nr4a-nuclear-receptor-nor1-in-hematopoietic-stem-cells-reduces-inflammation-but-not-abdominal-aortic-aneurysm-formation
#1
Hua Qing, Karrie L Jones, Elizabeth B Heywood, Hong Lu, Alan Daugherty, Dennis Bruemmer
BACKGROUND: The NR4A3 orphan nuclear hormone receptor, NOR1, functions as a constitutively active transcription factor to regulate inflammation, proliferation, and cell survival during pathological vascular remodeling. Inflammatory processes represent key mechanisms leading to abdominal aortic aneurysm (AAA) formation. However, a role of NOR1 in AAA formation has not been investigated previously. METHODS: Inflammatory gene expression was analyzed in bone marrow-derived macrophages isolated from NOR1-deficient mice...
October 18, 2017: BMC Cardiovascular Disorders
https://www.readbyqxmd.com/read/29026837/binding-site-analysis-of-the-caenorhabditis-elegans-nr4a-nuclear-receptor-nhr-6-during-development
#2
Brandon Praslicka, Jeremy S Harmson, Joohyun Kim, Vittobai Rashika Rangaraj, Aikseng Ooi, Chris R Gissendanner
Members of the NR4A subfamily of nuclear receptors make up a highly conserved, functionally diverse group of transcription factors implicated in a multitude of cellular processes such as proliferation, differentiation, apoptosis, metabolism and DNA repair. The gene nhr-6, which encodes the sole C. elegans NR4A nuclear receptor homolog, has a critical role in organogenesis and regulates the development of the spermatheca organ system. Our previous work revealed that nhr-6 is required for spermatheca cell divisions in late L3 and early L4 and spermatheca cell differentiation during the mid L4 stage...
2017: Nuclear Receptor Research
https://www.readbyqxmd.com/read/28951217/assessing-molecular-initiating-events-mies-key-events-kes-and-modulating-factors-mfs-for-styrene-responses-in-mouse-lungs-using-whole-genome-gene-expression-profiling-following-1-day-and-multi-week-exposures
#3
Melvin E Andersen, George Cruzan, Michael B Black, Salil N Pendse, Darol Dodd, James S Bus, Satinder S Sarang, Marcy I Banton, Robbie Waites, Patrick D McMullen
Styrene increased lung tumors in mice at chronic inhalation exposures of 20ppm and greater. MIEs, KEs and MFs were examined using gene expression in three strains of male mice (the parental C57BL/6 strain, a CYP2F2(-/-) knock out and a CYP2F2(-/-) transgenic containing human CYP2F1, 2A13 and 2B6). Exposures were for 1-day and 1, 4 and 26weeks. After 1-day exposures at 1, 5, 10, 20, 40 and 120ppm significant increases in differentially expressed genes (DEGs) occurred only in parental strain lungs where there was already an increase in DEGs at 5ppm and then many thousands of DEGs by 120ppm...
September 23, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28893954/the-orphan-nuclear-receptor-nr4a3-is-involved-in-the-function-of-dendritic-cells
#4
Masanori Nagaoka, Takuya Yashiro, Yuna Uchida, Tomoaki Ando, Mutsuko Hara, Hajime Arai, Hideoki Ogawa, Ko Okumura, Kazumi Kasakura, Chiharu Nishiyama
NR4A3/NOR1 belongs to the NR4A subfamily of the nuclear hormone receptor superfamily, which is activated in a ligand-independent manner. To examine the role of NR4A3 in gene expression of dendritic cells (DCs), we introduced NR4A3 small interfering RNA (siRNA) into bone marrow-derived DCs and determined the expression levels of mRNA and proteins of cytokines, cell surface molecules, NF-κB signaling-related proteins, and transcription factors. The expression level of NR4A3 was markedly upregulated by TLR-mediated stimulation in DCs...
October 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28844671/transcriptional-profiling-of-human-femoral-mesenchymal-stem-cells-in-osteoporosis-and-its-association-with-adipogenesis
#5
Yong Jun Choi, Insun Song, Yilan Jin, Hyun-Seok Jin, Hyung Min Ji, Seon-Yong Jeong, Ye-Yeon Won, Yoon-Sok Chung
Genetic alterations are major contributing factors in the development of osteoporosis. Osteoblasts and adipocytes share a common origin, mesenchymal stem cells (MSCs), and their genetic determinants might be important in the relationship between osteoporosis and obesity. In the present study, we aimed to isolate differentially expressed genes (DEGs) in osteoporosis and normal controls using human MSCs, and elucidate the common pathways and genes related to osteoporosis and adipogenesis. Human MSCs were obtained from the bone marrow of femurs from postmenopausal women during orthopedic surgeries...
October 20, 2017: Gene
https://www.readbyqxmd.com/read/28838938/nr4a-proteins-and-neutrophil-lifespan
#6
Lee-Ann H Allen
No abstract text is available yet for this article.
August 24, 2017: Blood
https://www.readbyqxmd.com/read/28808448/relevance-of-the-nr4a-sub-family-of-nuclear-orphan-receptors-in-trophoblastic-bewo-cell-differentiation
#7
Sudha Saryu Malhotra, Satish Kumar Gupta
Nur-77, a member of the NR4A sub-family of nuclear orphan receptors, is downregulated in the placentae of pre-eclamptic women. Here, we investigate the relevance of Nor-1, Nurr-1 and Nur-77 in trophoblastic cell differentiation. Their transcript levels were found to be significantly upregulated in BeWo cells treated with forskolin. The maximum increase was observed after 2 h, with a second peak in the expression levels after 48 h. The expression of NR4A sub-family members was also found to be upregulated in BeWo cells after treatment with hCG and GnRH...
2017: Cellular & Molecular Biology Letters
https://www.readbyqxmd.com/read/28804711/annotation-of-the-nuclear-receptors-in-an-estuarine-fish-species-fundulus-heteroclitus
#8
William S Baldwin, W Tyler Boswell, Gautam Ginjupalli, Elizabeth J Litoff
The nuclear receptors (NRs) are ligand-dependent transcription factors that respond to various internal as well as external cues such as nutrients, pheromones, and steroid hormones that play crucial roles in regulation and maintenance of homeostasis and orchestrating the physiological and stress responses of an organism. We annotated the Fundulus heteroclitus (mummichog; Atlantic killifish) nuclear receptors. Mummichog are a non-migratory, estuarine fish with a limited home range often used in environmental research as a field model for studying ecological and evolutionary responses to variable environmental conditions such as salinity, oxygen, temperature, pH, and toxic compounds because of their hardiness...
2017: Nuclear Receptor Research
https://www.readbyqxmd.com/read/28717175/snake-venom-vegf-vammin-induces-a-highly-efficient-angiogenic-response-in-skeletal-muscle-via-vegfr-2-nrp-specific-signaling
#9
Pyry I Toivanen, Tiina Nieminen, Johanna P Laakkonen, Tommi Heikura, Minna U Kaikkonen, Seppo Ylä-Herttuala
Vascular Endothelial Growth Factors (VEGFs) are promising molecules for the treatment of ischemic diseases by pro-angiogenic therapy. Snake venom VEGFs are a novel subgroup with unique receptor binding profiles and as such are potential new therapeutic agents. We determined the ligand-receptor interactions, gene regulation and angiogenic properties of Vipera ammodytes venom VEGF, Vammin, and compared it to the canonical angiogenic factor VEGF-A to evaluate the use of Vammin for therapeutic angiogenesis. Vammin efficiently induced VEGFR-2 mediated proliferation and expression of genes associated with proliferation, migration and angiogenesis...
July 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28709726/induction-and-maintenance-of-regulatory-t-cells-by-transcription-factors-and-epigenetic-modifications
#10
REVIEW
Mana Iizuka-Koga, Hiroko Nakatsukasa, Minako Ito, Takashi Akanuma, Qianjin Lu, Akihiko Yoshimura
Regulatory T cells (Tregs) are an essential cell subset for the maintenance of immune homeostasis. Foxp3 (Forkhead box P3) is the Treg master gene which is essential for immune suppressing activity. In addition, Tregs are characterized by a distinct pattern of gene expression, including upregulation of immune-suppressive genes and silencing of inflammatory genes. The molecular mechanisms of Treg development and maintenance have been intensively investigated. Tregs are characterized by expression of the transcription factor Foxp3...
July 11, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28637666/nr4a-orphan-nuclear-receptor-family-members-nr4a2-and-nr4a3-regulate-neutrophil-number-and-survival
#11
Lynne R Prince, Svenja D Prosseda, Kathryn Higgins, Jennifer Carlring, Elizabeth C Prestwich, Nikolay V Ogryzko, Atiqur Rahman, Alexander Basran, Francesco Falciani, Philip Taylor, Stephen A Renshaw, Moira K B Whyte, Ian Sabroe
The lifespan of neutrophils is plastic and highly responsive to factors that regulate cellular survival. Defects in neutrophil number and survival are common to both hematologic disorders and chronic inflammatory diseases. At sites of inflammation, neutrophils respond to multiple signals that activate protein kinase A (PKA) signaling, which positively regulates neutrophil survival. The aim of this study was to define transcriptional responses to PKA activation and to delineate the roles of these factors in neutrophil function and survival...
August 24, 2017: Blood
https://www.readbyqxmd.com/read/28607424/benzo-a-pyrene-triggers-desensitization-of-%C3%AE-2-adrenergic-pathway
#12
Abdullah Mayati, Normand Podechard, Manuelle Rineau, Lydie Sparfel, Dominique Lagadic-Gossmann, Olivier Fardel, Eric Le Ferrec
Exposure to environmental polycyclic aromatic hydrocarbons (PAHs), such as benzo(a)pyrene (B(a)P), has been linked to several health-threatening risks. PAHs were also shown to hinder adrenergic receptor (ADR) responses. As we previously demonstrated that B(a)P can directly interact with the β2ADR, we investigated here whether B(a)P could decrease β2ADR responsiveness by triggering receptor desensitization phenomena. We firstly showed that exposure to B(a)P reduced β2ADR-mediated epinephrine-induced induction of NR4A gene mRNAs and of intracellular cAMP...
June 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28607006/nr4a2-promotes-dna-double-strand-break-repair-upon-exposure-to-uvr
#13
Kelvin Yin, Yash Chhabra, Romain Tropée, Yi Chieh Lim, Mitchell Fane, Eloise Dray, Richard A Sturm, Aaron G Smith
Exposure of melanocytes to ultraviolet radiation (UVR) induces the formation of UV lesions that can produce deleterious effects in genomic DNA. Encounters of replication forks with unrepaired UV lesions can lead to several complex phenomena, such as the formation of DNA double-strand breaks (DSBs). The NR4A family of nuclear receptors are transcription factors that have been associated with mediating DNA repair functions downstream of the MC1R signaling pathway in melanocytes. In particular, emerging evidence shows that upon DNA damage, the NR4A2 receptor can translocate to sites of UV lesion by mechanisms requiring post-translational modifications within the N-terminal domain and at a serine residue in the DNA-binding domain at position 337...
June 12, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28352330/orphan-nuclear-receptor-nurr1-as-a-potential-novel-marker-for-progression-in-human-pancreatic-ductal-adenocarcinoma
#14
Li Ji, Chen Gong, Liangyu Ge, Linping Song, Fenfen Chen, Chunjing Jin, Hongyan Zhu, Guoxiong Zhou
Nuclear receptor related-1 protein (Nurr1) is a novel orphan member of the nuclear receptor superfamily (the NR4A family) involved in tumorigenesis. The aim of the present study was to investigate the expression and possible function of Nurr1 in pancreatic ductal adenocarcinoma (PDAC). The expression pattern of Nurr1 protein was determined using immunohistochemical staining in 138 patients with PDAC. Elevated Nurr1 expression was more commonly observed in PDAC tissues and cell lines compared with healthy controls...
February 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28317936/priming-of-transcriptional-memory-responses-via-the-chromatin-accessibility-landscape-in-t-cells
#15
Wen Juan Tu, Kristine Hardy, Christopher R Sutton, Robert McCuaig, Jasmine Li, Jenny Dunn, Abel Tan, Vedran Brezar, Melanie Morris, Gareth Denyer, Sau Kuen Lee, Stephen J Turner, Nabila Seddiki, Corey Smith, Rajiv Khanna, Sudha Rao
Memory T cells exhibit transcriptional memory and "remember" their previous pathogenic encounter to increase transcription on re-infection. However, how this transcriptional priming response is regulated is unknown. Here we performed global FAIRE-seq profiling of chromatin accessibility in a human T cell transcriptional memory model. Primary activation induced persistent accessibility changes, and secondary activation induced secondary-specific opening of previously less accessible regions associated with enhanced expression of memory-responsive genes...
March 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28283662/exhaustion-associated-regulatory-regions-in-cd8-tumor-infiltrating-t-cells
#16
Giuliana P Mognol, Roberto Spreafico, Victor Wong, James P Scott-Browne, Susan Togher, Alexander Hoffmann, Patrick G Hogan, Anjana Rao, Sara Trifari
T-cell exhaustion is a progressive loss of effector function and memory potential due to persistent antigen exposure, which occurs in chronic viral infections and cancer. Here we investigate the relation between gene expression and chromatin accessibility in CD8(+) tumor-infiltrating lymphocytes (TILs) that recognize a model tumor antigen and have features of both activation and functional exhaustion. By filtering out accessible regions observed in bystander, nonexhausted TILs and in acutely restimulated CD8(+) T cells, we define a pattern of chromatin accessibility specific for T-cell exhaustion, characterized by enrichment for consensus binding motifs for Nr4a and NFAT transcription factors...
March 28, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28249906/nr4a3-suppresses-lymphomagenesis-through-induction-of-proapoptotic-genes
#17
Alexander J A Deutsch, Beate Rinner, Martin Pichler, Katharina Prochazka, Katrin Pansy, Marco Bischof, Karoline Fechter, Stefan Hatzl, Julia Feichtinger, Kerstin Wenzl, Marie-Therese Frisch, Verena Stiegelbauer, Andreas Prokesch, Anne Krogsdam, Heinz Sill, Gerhard G Thallinger, Hildegard T Greinix, Chenguang Wang, Christine Beham-Schmid, Peter Neumeister
Nuclear orphan receptor NR4A1 exerts an essential tumor suppressor function in aggressive lymphomas. In this study, we investigated the hypothesized contribution of the related NR4A family member NR4A3 to lymphomagenesis. In aggressive lymphoma patients, low expression of NR4A3 was associated with poor survival. Ectopic expression or pharmacological activation of NR4A3 in lymphoma cell lines led to a significantly higher proportion of apoptotic cells. In a mouse NSG xenograft model of lymphoma (stably transduced SuDHL4 cells), NR4A3 expression abrogated tumor growth, compared with vector control and uninduced cells that formed massive tumors...
May 1, 2017: Cancer Research
https://www.readbyqxmd.com/read/28198082/pck1-expression-is-correlated-with-the-plasma-glucose-level-in-the-duck
#18
L Chen, T Zeng, G Q Li, R Liu, Y Tian, Q H Li, L Z Lu
Phosphoenolpyruvate carboxykinase 1 (soluble) (PCK1) is a key gene in gluconeogenesis and glyceroneogenesis. Although its functions have been extensively studied in mice, bats and humans, little is known in ducks. Here, PCK1 functions were studied using a duck domestication model and a 48-h fasting experiment. We found PCK1 expression significantly decreased in two breeds of domestic ducks (Jinyun Pockmark ducks and Cherry Valley ducks) as compared with wild ducks (Anas platyrhynchos). Simultaneously, plasma levels of glucose, triglycerides and free fatty acid in domestic ducks were lower than in wild ducks...
June 2017: Animal Genetics
https://www.readbyqxmd.com/read/28167941/nr4a-receptors-differentially-regulate-nf-%C3%AE%C2%BAb-signaling-in-myeloid-cells
#19
Caitriona McEvoy, Monica de Gaetano, Hugh E Giffney, Bojlul Bahar, Eoin P Cummins, Eoin P Brennan, Mary Barry, Orina Belton, Catherine G Godson, Evelyn P Murphy, Daniel Crean
Dysregulation of inflammatory responses is a hallmark of multiple diseases such as atherosclerosis and rheumatoid arthritis. As constitutively active transcription factors, NR4A nuclear receptors function to control the magnitude of inflammatory responses and in chronic inflammatory disease can be protective or pathogenic. Within this study, we demonstrate that TLR4 stimulation using the endotoxin lipopolysaccharide (LPS) rapidly enhances NR4A1-3 expression in human and murine, primary and immortalized myeloid cells with concomitant gene transcription and protein secretion of MIP-3α, a central chemokine implicated in numerous pathologies...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28055275/the-nr4a-subfamily-of-nuclear-receptors-potential-new-therapeutic-targets-for-the-treatment-of-inflammatory-diseases
#20
REVIEW
Ricardo Rodríguez-Calvo, Marta Tajes, Manuel Vázquez-Carrera
Prolonged inflammatory response contributes to the pathogenesis of chronic disease-related disturbances. Among nuclear receptors (NRs), the orphan NR4A subfamily, which includes Nur77 (NR4A1), Nurr1 (NR4A2) and NOR1 (NR4A3), has recently emerged as a therapeutic target for the treatment of inflammation. Areas covered: This review focuses on the capacity of NR4A receptors to counter-regulate the development of the inflammatory response, with a special focus on the molecular transrepression mechanisms. Expert opinion: Recent studies have highlighted the role of NR4A receptors as significant regulators of the inflammatory response...
March 2017: Expert Opinion on Therapeutic Targets
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