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https://www.readbyqxmd.com/read/29559474/inhibition-of-nr4a-receptors-enhances-anti-tumor-immunity-by-breaking-treg-mediated-immune-tolerance
#1
Sana Hibino, Shunsuke Chikuma, Taisuke Kondo, Minako Ito, Hiroko Nakatsukasa, Setsuko Omata-Mise, Akihiko Yoshimura
Enhanced infiltration of regulatory T (Treg) cells into tumor tissue is detrimental to cancer patients and closely associated with poor prognosis as they create an immunosuppressive state that suppresses anti-tumor immune responses. Therefore, breaking Treg-mediated immune tolerance is important when considering cancer immunotherapy. Here we show that the Nr4a nuclear receptors, key transcription factors maintaining Treg cell genetic programs, contribute to Treg-mediated suppression of anti-tumor immunity in the tumor microenvironment...
March 20, 2018: Cancer Research
https://www.readbyqxmd.com/read/29531824/nr4a2-protects-cardiomyocytes-against-myocardial-infarction-injury-by-promoting-autophagy
#2
Honghong Liu, Pingping Liu, Xingxing Shi, Deling Yin, Jing Zhao
Myocardial infarction (MI), characterized by ischemia-induced cardiomyocyte apoptosis, is the leading cause of mortality worldwide. NR4A2, a member of the NR4A orphan nucleus receptor family, is upregulated in mouse hearts with MI injury. Furthermore, NR4A2 knockdown aggravates heart injury as evidenced by enlarged hearts and increased apoptosis. To elucidate the underlying mechanisms of NR4A2-regulated apoptosis, we used H9c2 cardiomyocytes deprived of serum and neonatal rat cardiomyocytes (NRCMs) exposed to hypoxia to mimic ischemic conditions in vivo...
December 2018: Cell Death Discovery
https://www.readbyqxmd.com/read/29527211/the-footprints-of-poly-autoimmunity-evidence-for-common-biological-factors-involved-in-multiple-sclerosis-and-hashimoto-s-thyroiditis
#3
Simona Perga, Serena Martire, Francesca Montarolo, Ilaria Giordani, Michela Spadaro, Gabriele Bono, Stefania Corvisieri, Ilaria Messuti, Giancarlo Panzica, Fabio Orlandi, Antonio Bertolotto
Autoimmune diseases are a diverse group of chronic disorders and affect a multitude of organs and systems. However, the existence of common pathophysiological mechanisms is hypothesized and reports of shared risk are emerging as well. In this regard, patients with multiple sclerosis (MS) have been shown to have an increased susceptibility to develop chronic autoimmune thyroid diseases, in particular Hashimoto's thyroiditis (HT), suggesting an autoimmune predisposition. However, studies comparing such different pathologies of autoimmune origin are still missing till date...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29526770/hr38-an-ortholog-of-nr4a-family-nuclear-receptors-mediates-20-hydroxyecdysone-regulation-of-carbohydrate-metabolism-during-mosquito-reproduction
#4
Dujuan Dong, Yang Zhang, Vlastimil Smykal, Lin Ling, Alexander S Raikhel
The Aedes aegypti mosquito is the principal vector for many dangerous human viral diseases. Carbohydrate metabolism (CM) is essential for supplying the energy necessary for host seeking, blood digestion and rapid egg development of this vector insect. The steroid hormone 20-hydroxyecdysone (20E) and the ecdysone receptor (EcR) are important regulators of CM, coordinating it with female reproductive events. We report here that the NR4A nuclear receptor AHR38 plays a critical role in mediating these actions of 20E and EcR...
March 8, 2018: Insect Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/29448246/effect-of-mst1-on-endometriosis-apoptosis-and-migration-role-of-drp1-related-mitochondrial-fission-and-parkin-required-mitophagy
#5
Qingdong Zhao, Mingxia Ye, Wen Yang, Min Wang, Mingxia Li, Chenglei Gu, Luyang Zhao, Zhe Zhang, Weidong Han, Wensheng Fan, Yuanguang Meng
BACKGROUND/AIMS: Mitochondrial homeostasis is implicated in the development and progression of endometriosis through poorly defined mechanisms. Mst1 is the major growth suppressor related to cancer migration, apoptosis and proliferation. However, whether Mst1 is involved in endometriosis apoptosis and migration via regulating the mitochondrial function remains to be elucidated. METHODS: Expression of Mst1 in endometriosis was examined via western blots. Cellular apoptosis was detected via MTT and TUNEL assay...
2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29368971/ligand-dependent-transcriptional-induction-of-lethal-autophagy-a-new-perspective-for-cancer-treatment
#6
Sandrine Silvente-Poirot, Gregory Ségala, Mathias C Poirot, Marc Poirot
Dendrogenin A (DDA) is a mammalian metabolite that displays anticancer and chemopreventive properties in mice. At the cancer cell level, DDA induces differentiation and death. We investigated herein the nature of DDA cytoxicity in cancer cells. We showed that DDA triggers biochemical and cellular features of macroautophagy/autophagy and that autophagy is cytotoxic. DDA induces both the accumulation of pro-lysosomal sterols and stimulates the expression of regulators of autophagy such as NR4A, LC3 and TFEB through binding to the liver X receptor (LXR), a ligand-dependent transcription factor consisting of 2 isoforms, NR1H2 and NR1H3...
January 25, 2018: Autophagy
https://www.readbyqxmd.com/read/29343483/nr4a1-and-nr4a3-restrict-hsc-proliferation-via-reciprocal-regulation-of-c-ebp%C3%AE-and-inflammatory-signaling
#7
Pablo R Freire, Orla M Conneely
Members of the NR4A subfamily of nuclear receptors have complex, overlapping roles during hematopoietic cell development and also function as tumor suppressors of hematologic malignancies. We previously identified NR4A1 and NR4A3 (NR4A1/3) as functionally redundant suppressors of acute myeloid leukemia (AML) development. However, their role in hematopoietic stem cell (HSC) homeostasis remains to be disclosed. Using a conditional Nr4a1 / Nr4a3 knockout mouse (CDKO), we show that codepletion of NR4A1/3 promotes acute changes in HSC homeostasis including loss of HSC quiescence, accumulation of oxidative stress, and DNA damage while maintaining stem cell regenerative and differentiation capacity...
March 8, 2018: Blood
https://www.readbyqxmd.com/read/29145494/global-analysis-of-gene-expression-mediated-by-ox1-orexin-receptor-signaling-in-a-hypothalamic-cell-line
#8
Eric Koesema, Thomas Kodadek
The orexins and their cognate G-protein coupled receptors have been widely studied due to their associations with various behaviors and cellular processes. However, the detailed downstream signaling cascades that mediate these effects are not completely understood. We report the generation of a neuronal model cell line that stably expresses the OX1 orexin receptor (OX1) and an RNA-Seq analysis of changes in gene expression seen upon receptor activation. Upon treatment with orexin, several families of related transcription factors are transcriptionally regulated, including the early growth response genes (Egr), the Kruppel-like factors (Klf), and the Nr4a subgroup of nuclear hormone receptors...
2017: PloS One
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
#9
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
#10
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
#11
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...
November 15, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28893954/the-orphan-nuclear-receptor-nr4a3-is-involved-in-the-function-of-dendritic-cells
#12
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
#13
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
#14
COMMENT
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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