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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
#1
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
#2
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
#3
Lynne R Prince, Svenja Dannewitz 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
Neutrophil lifespan 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...
June 21, 2017: Blood
https://www.readbyqxmd.com/read/28607424/benzo-a-pyrene-triggers-desensitization-of-%C3%AE-2-adrenergic-pathway
#4
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
#5
Kelvin Yin, Yash Chhabra, Romain Tropée, Yi Chieh Lim, Mitchell Fane, Eloise Dray, Richard 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 signalling 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 biding 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
#6
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
#7
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
#8
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
#9
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...
March 1, 2017: Cancer Research
https://www.readbyqxmd.com/read/28198082/pck1-expression-is-correlated-with-the-plasma-glucose-level-in-the-duck
#10
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
#11
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
#12
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
https://www.readbyqxmd.com/read/27992436/transcriptomic-analysis-shows-decreased-cortical-expression-of-nr4a1-nr4a2-and-rxrb-in-schizophrenia-and-provides-evidence-for-nuclear-receptor-dysregulation
#13
Susan M Corley, Shan-Yuan Tsai, Marc R Wilkins, Cynthia Shannon Weickert
Many genes are differentially expressed in the cortex of people with schizophrenia, implicating factors that control transcription more generally. Hormone nuclear receptors dimerize to coordinate context-dependent changes in gene expression. We hypothesized that members of two families of nuclear receptors (NR4As), and retinoid receptors (RARs and RXRs), are altered in the dorsal lateral prefrontal cortex (DLPFC) of people with schizophrenia. We used next generation sequencing and then qPCR analysis to test for changes in mRNA levels for transcripts encoding nuclear receptors: orphan nuclear receptors (3 in the NR4A, 3 in the RAR, 3 in the RXR families and KLF4) in total RNA extracted from the DLPFC from people with schizophrenia compared to controls (n = 74)...
2016: PloS One
https://www.readbyqxmd.com/read/27939672/dynamic-changes-in-chromatin-accessibility-occur-in-cd8-t-cells-responding-to-viral-infection
#14
James P Scott-Browne, Isaac F López-Moyado, Sara Trifari, Victor Wong, Lukas Chavez, Anjana Rao, Renata M Pereira
In response to acute infection, naive CD8(+) T cells expand, differentiate into effector cells, and then contract to a long-lived pool of memory cells after pathogen clearance. During chronic infections or in tumors, CD8(+) T cells acquire an "exhausted" phenotype. Here we present genome-wide comparisons of chromatin accessibility and gene expression from endogenous CD8(+) T cells responding to acute and chronic viral infection using ATAC-seq and RNA-seq techniques. Acquisition of effector, memory, or exhausted phenotypes was associated with stable changes in chromatin accessibility away from the naive T cell state...
December 20, 2016: Immunity
https://www.readbyqxmd.com/read/27913963/erratum-to-altered-nr4a-subfamily-gene-expression-level-in-peripheral-blood-of-parkinson-s-and-alzheimer-s-disease-patients
#15
Francesca Montarolo, Simona Perga, Serena Martire, De'sire'e Nicole Navone, Alberto Marchet, Daniela Leotta, Antonio Bertolotto
No abstract text is available yet for this article.
December 2, 2016: Neurotoxicity Research
https://www.readbyqxmd.com/read/27871853/nur77-downregulation-triggers-pulmonary-artery-smooth-muscle-cell-proliferation-and-migration-in-mice-with-hypoxic-pulmonary-hypertension-via-the-axin2-%C3%AE-catenin-signaling-pathway
#16
Xiaowei Nie, Jianxin Tan, Youai Dai, Wenjun Mao, Yuan Chen, Guowei Qin, Guirong Li, Chenyou Shen, Jingjing Zhao, Jingyu Chen
Pulmonary arterial hypertension (PAH) is a life-threatening disease characterized by remodeling of the pulmonary vasculature, including marked proliferation and reduced apoptosis of pulmonary artery smooth muscle cells (PASMCs). Members of the nuclear receptor 4A (NR4A) subfamily are involved in a variety of biological events, such as cell apoptosis, proliferation, inflammation, and metabolism. Activation of Nur77 (an orphan nuclear receptor that belongs to NR4A subfamily) has recently been reported to be as a beneficial agent in the treatment of cardiovascular and metabolic diseases...
December 2016: Vascular Pharmacology
https://www.readbyqxmd.com/read/27834392/pharmacological-activators-of-the-nr4a-nuclear-receptors-enhance-ltp-in-a-creb-cbp-dependent-manner
#17
Morgan S Bridi, Joshua D Hawk, Snehajyoti Chatterjee, Stephen Safe, Ted Abel
Nr4a nuclear receptors contribute to long-term memory formation and are required for long-term memory enhancement by a class of broad-acting drugs known as histone deacetylase (HDAC) inhibitors. Understanding the molecular mechanisms that regulate these genes and identifying ways to increase their activity may provide novel therapeutic approaches for ameliorating cognitive dysfunction. In the present study, we find that Nr4a gene expression after learning requires the cAMP-response element binding (CREB) interaction domain of the histone acetyltransferase CREB-binding protein (CBP)...
May 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/27820700/the-transcription-factor-nr4a3-controls-cd103-dendritic-cell-migration
#18
Kiwon Park, Zbigniew Mikulski, Goo-Young Seo, Aleksander Y Andreyev, Paola Marcovecchio, Amy Blatchley, Mitchell Kronenberg, Catherine C Hedrick
The transcription factor NR4A3 (also known as NOR-1) is a member of the Nr4a family of nuclear receptors and is expressed in myeloid and lymphoid cells. Here, we have shown that Nr4a3 is essential for the migration of CD103+ dendritic cells (DCs) to lymph nodes (LNs). Nr4a3-deficient mice had very few CD103+ migratory DCs (mDCs) present in LNs, and mixed-chimera studies revealed that this migratory defect was cell intrinsic. We further found that CD103+ DCs from Nr4a3-deficient mice displayed a marked loss of surface expression of the chemokine CCR7...
December 1, 2016: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/27646469/adenovirus-mediated-expression-of-orphan-nuclear-receptor-nr4a2-targeting-hepatic-stellate-cell-attenuates-liver-fibrosis-in-rats
#19
Pengguo Chen, Jie Li, Yan Huo, Jin Lu, Lili Wan, Quanjun Yang, Jinlu Huang, Run Gan, Cheng Guo
Liver fibrosis is a wound-healing response characterized with the accumulation of extracellular matrix (ECM). And hepatic stellate cells (HSCs) are the principal cell source of ECM. NR4A2 (Nurr1) is a member of orphan nuclear receptor NR4A family and acts as transcription factor. It participates in regulating cell differentiation, proliferation and apoptosis. We previously demonstrated that NR4A2 expression in fibrotic liver reduced significantly compared with normal liver and NR4A2 knockout in HSCs promoted ECM production...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27587263/crtc1-function-during-memory-encoding-is-disrupted-in-neurodegeneration
#20
Arnaldo Parra-Damas, Meng Chen, Lilian Enriquez-Barreto, Laura Ortega, Sara Acosta, Judith Camats Perna, M Neus Fullana, José Aguilera, José Rodríguez-Alvarez, Carlos A Saura
BACKGROUND: Associative memory impairment is an early clinical feature of dementia patients, but the molecular and cellular mechanisms underlying these deficits are largely unknown. In this study, we investigated the functional regulation of the cyclic adenosine monophosphate response element binding protein (CREB)-regulated transcription coactivator 1 (CRTC1) by associative learning in physiological and neurodegenerative conditions. METHODS: We evaluated the activation of CRTC1 in the hippocampus of control mice and mice lacking the Alzheimer's disease-linked presenilin genes (presenilin conditional double knockout [PS cDKO]) after one-trial contextual fear conditioning by using biochemical, immunohistochemical, and gene expression analyses...
January 15, 2017: Biological Psychiatry
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