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nuclear receptor subfamily 4

Hyelin Na, Ho Lee, Min-Ho Lee, Han Jeong Lim, Hyeon-Ji Kim, Yoon Jeon, Hae-Lim Kang, Mi-Ock Lee
AIMS: To elucidate the role of nuclear receptor subfamily 1, group D, member 1 (Nr1d1) in hepatic lipid metabolism and pathogenesis of nonalcoholic fatty liver diseases, Nr1d1 gene mutant mice, in which the DNA-binding domain (exons 3 and 4) was deleted (Nr1d1 Δex3/4), were challenged with a high-fat diet (HFD), and the gene expression patterns that responded to this alteration were profiled. MAIN METHODS: The Nr1d1 Δex3/4 mice were fed an HFD for 12weeks. Liver tissues were examined by histology, and lipid droplets were detected by Oil-Red O staining...
October 5, 2016: Life Sciences
Takashi Yazawa, Yoshitaka Imamichi, Kaoru Miyamoto, Md Rafiqul Islam Khan, Junsuke Uwada, Akihiro Umezawa, Takanobu Taniguchi
Steroid hormones are mainly produced in adrenal glands and gonads. Because steroid hormones play vital roles in various physiological processes, replacement of deficient steroid hormones by hormone replacement therapy (HRT) is necessary for patients with adrenal and gonadal failure. In addition to HRT, tissue regeneration using stem cells is predicted to provide novel therapy. Among various stem cell types, mesenchymal stem cells can be differentiated into steroidogenic cells following ectopic expression of nuclear receptor (NR) 5A subfamily proteins, steroidogenic factor-1 (also known as adrenal 4 binding protein) and liver receptor homolog-1, with the aid of cAMP signaling...
September 29, 2016: Endocrine Journal
Jiantao Zhang, Wenli Zhou, Ying Liu, Nan Li
Down syndrome (DS) is the most common birth defect in children. To investigate the mechanisms of DS, the present study analyzed the bisulfite‑sequencing (seq) data GSE42144, which was downloaded from the Gene Expression Omnibus. GSE42144 included DNA methylation data of three DS samples and three control samples, and RNA‑seq data of two DS samples and five control samples. The methylated sites in the bisulfite‑seq data were detected using Bismark and Bowtie2. The BiSeq tool was applied to determine differentially methylated regions and to identify adjacent genes...
September 26, 2016: Molecular Medicine Reports
Chandra Sekhar Boddupalli, Shiny Nair, Simon M Gray, Heba N Nowyhed, Rakesh Verma, Joanna A Gibson, Clara Abraham, Deepak Narayan, Juan Vasquez, Catherine C Hedrick, Richard A Flavell, Kavita M Dhodapkar, Susan M Kaech, Madhav V Dhodapkar
Immune surveillance in tissues is mediated by a long-lived subset of tissue-resident memory T cells (Trm cells). A putative subset of tissue-resident long-lived stem cells is characterized by the ability to efflux Hoechst dyes and is referred to as side population (SP) cells. Here, we have characterized a subset of SP T cells (Tsp cells) that exhibit a quiescent (G0) phenotype in humans and mice. Human Trm cells in the gut and BM were enriched in Tsp cells that were predominantly in the G0 stage of the cell cycle...
October 3, 2016: Journal of Clinical Investigation
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...
July 11, 2016: Biological Psychiatry
Yng-Tay Chen, Jiunn-Wang Liao, Ya-Ching Tsai, Fuu-Jen Tsai
Our previous genome-wide association studies showed that DNA methyltransferase 1 (DNMT1) is associated with increased susceptibility to type 2 diabetes (T2D) in Han Chinese individuals. Here, we aimed to further evaluate the role of DNMT1 in T2D. We performed a genome-wide DNA methylation array and found that the nuclear receptor subfamily 4 group A member 1 (NR4A1) promoter was hypermethylated in patients with T2D and in a mouse model of T2D. Moreover, DNA hypermethylation of the NR4A1 promoter reduced NR4A1 mRNA expression...
June 14, 2016: Oncotarget
Maija Suvanto, Timo Jahnukainen, Marjo Kestilä, Hannu Jalanko
Polymorphic variants in several molecules involved in the glomerular function and drug metabolism have been implicated in the pathophysiology of pediatric idiopathic nephrotic syndrome (INS), but the results remain inconsistent. We analyzed the association of eleven allelic variants in eight genes (angiopoietin-like 4 (ANGPTL4), glypican 5 (GPC5), interleukin-13 (IL-13), macrophage migration inhibitory factor (MIF), neural nitric oxide synthetase (nNOS), multidrug resistance-1 (MDR1), glucocorticoid-induced transcript-1 (GLCCI1), and nuclear receptor subfamily-3 (NR3C1)) in 100 INS patients followed up till adulthood...
2016: International Journal of Nephrology
Jordan A Beard, Alexa Tenga, Justin Hills, Jessica D Hoyer, Milu T Cherian, Yong-Dong Wang, Taosheng Chen
Nuclear receptor subfamily 4 group A member 2 (NR4A2) is an orphan nuclear receptor that is over-expressed in cancer and promotes cell proliferation, migration, transformation, and chemoresistance. Increased expression and function of NR4A2 have been attributed to various signaling pathways, but little is known about microRNA (miRNA) regulation of NR4A2 in cancer. To investigate the posttranscriptional regulation of NR4A2, we used a 3' untranslated region (UTR) reporter screen and identified miR-34 as a putative regulator of NR4A2...
2016: Scientific Reports
Armando G Salinas, Margaret I Davis, David M Lovinger, Yolanda Mateo
The striatum is typically classified according to its major output pathways, which consist of dopamine D1 and D2 receptor-expressing neurons. The striatum is also divided into striosome and matrix compartments, based on the differential expression of a number of proteins, including the mu opioid receptor, dopamine transporter (DAT), and Nr4a1 (nuclear receptor subfamily 4, group A, member 1). Numerous functional differences between the striosome and matrix compartments are implicated in dopamine-related neurological disorders including Parkinson's disease and addiction...
September 2016: Neuropharmacology
Victoria Klepsch, Natascha Hermann-Kleiter, Gottfried Baier
Blockade of immune checkpoints has emerged as key strategy in the development of effective cancer therapies. In contrast to cell surface checkpoints like CTLA-4 and PD-1, however, additional cancer therapeutic targets are located inside the effector immune cells. Targeting these alternative checkpoints in cancer immunotherapy with the goal to strengthen the patient's immune system are likely to extend the benefits of cancer immunotherapy in the near future. Along this line, we have defined and validated the orphan nuclear receptor NR2F6 (nuclear receptor subfamily 2 group F member 6, also called Ear-2) as an intracellular immune checkpoint in effector T cells...
October 2016: Immunology Letters
Wan-Ning Wang, Wen-Long Zhang, Guang-Yu Zhou, Fu-Zhe Ma, Tao Sun, Sen-Sen Su, Zhong-Gao Xu
In this study, we aimed to explore the molecular mechanisms of and genetic factors influencing diabetic nephropathy (DN). Gene expression profiles associated with DN were obtained from the GEO database (Accession no. GSE20844). The differentially expressed genes (DEGs) between diabetic mice and non-diabetic mice were screened. Subsequently, the DEGs were subjected to functional and pathway analysis. The protein-protein interaction (PPI) network was constructed and the transcription factors (TFs) were screened among the DEGs...
May 2016: International Journal of Molecular Medicine
Sajjad Karim, Zeenat Mirza, Adeel G Chaudhary, Adel M Abuzenadah, Mamdooh Gari, Mohammed H Al-Qahtani
Toxicity induced by radiation therapy is a curse for cancer patients undergoing treatment. It is imperative to understand and define an ideal condition where the positive effects notably outweigh the negative. We used a microarray meta-analysis approach to measure global gene-expression before and after radiation exposure. Bioinformatic tools were used for pathways, network, gene ontology and toxicity related studies. We found 429 differentially expressed genes at fold change >2 and p-value <0.05. The most significantly upregulated genes were synuclein alpha (SNCA), carbonic anhydrase I (CA1), X-linked Kx blood group (XK), glycophorin A and B (GYPA and GYPB), and hemogen (HEMGN), while downregulated ones were membrane-spanning 4-domains, subfamily A member 1 (MS4A1), immunoglobulin heavy constant mu (IGHM), chemokine (C-C motif) receptor 7 (CCR7), BTB and CNC homology 1 transcription factor 2 (BACH2), and B-cell CLL/lymphoma 11B (BCL11B)...
2016: International Journal of Molecular Sciences
Yuan Gao, Guo-xian Qi, Liang Guo, Ying-xian Sun
BACKGROUND: We aimed to predict key genes associated with acute myocardial infarction (AMI) by bioinformatics analysis. METHODS: The microarray data of GSE48060, including peripheral blood samples from 31 first-time AMI patients within 48-h post-MI and 21 normal controls, were obtained from Gene Expression Omnibus database. The differentially expressed genes (DEGs) in AMI samples compared with normal controls were identified. Functional enrichment analysis was then performed, followed by analysis of protein-protein interaction (PPI) network and transcription regulatory network (TRN)...
April 2016: Cardiovascular Therapeutics
Chenfang Zhu, Liu He, Xin Zhou, Xin Nie, Yan Gu
In previous studies Sulf2 has been evidenced to play an important role in tumor progression through editing sulfate moieties on heparan sulfate proteoglycans (HSPGs) and modulating heparin binding growth factors. However, the role of Sulf2 in breast cancer progression is still poorly understood. In the present study, we hypothesized that Sulf2 promoted breast cancer progression. Two different breast cancer cell lines, MCF-7 and MDA-MB-231, were chosen for this study because of high and low Sulf2 expression levels...
March 2016: Oncology Reports
Fei Su, Desi Shang, Yanjun Xu, Li Feng, Haixiu Yang, Baoquan Liu, Shengyang Su, Lina Chen, Xia Li
Dissecting the characteristics of the transcription factor (TF) regulatory subpathway is helpful for understanding the TF underlying regulatory function in complex biological systems. To gain insight into the influence of TFs on their regulatory subpathways, we constructed a global TF-subpathways network (TSN) to analyze systematically the regulatory effect of common-motif, common-family, or common-tissue TFs on subpathways. We performed cluster analysis to show that the common-motif, common-family, or common-tissue TFs that regulated the same pathway classes tended to cluster together and contribute to the same biological function that led to disease initiation and progression...
2015: BioMed Research International
T Kumchoo, S Mekchay
The nuclear receptor subfamily 4, group A, member 1 (NR4A1) and guanine nucleotide binding protein beta polypeptide 2 like-1 (GNB2L1) genes are expressed during the ovulatory process and in early pregnancy in pigs. The objective of this study was to analyze the effects of NR4A1 and GNB2L1 gene variants on reproductive traits in commercial pig breeds. Two single nucleotide polymorphisms (SNPs) of NR4A1 and GNB2L1 were identified by a polymerase chain reaction-restriction fragment length polymorphism method. Analysis of the association of these two SNPs with reproductive traits was evaluated in 515 commercial sows (273 Large White and 242 Landrace)...
2015: Genetics and Molecular Research: GMR
Neema Yazdani, Clarissa C Parker, Ying Shen, Eric R Reed, Michael A Guido, Loren A Kole, Stacey L Kirkpatrick, Jackie E Lim, Greta Sokoloff, Riyan Cheng, W Evan Johnson, Abraham A Palmer, Camron D Bryant
Psychostimulant addiction is a heritable substance use disorder; however its genetic basis is almost entirely unknown. Quantitative trait locus (QTL) mapping in mice offers a complementary approach to human genome-wide association studies and can facilitate environment control, statistical power, novel gene discovery, and neurobiological mechanisms. We used interval-specific congenic mouse lines carrying various segments of chromosome 11 from the DBA/2J strain on an isogenic C57BL/6J background to positionally clone a 206 kb QTL (50,185,512-50,391,845 bp) that was causally associated with a reduction in the locomotor stimulant response to methamphetamine (2 mg/kg, i...
December 2015: PLoS Genetics
Ornella I Selmin, Changming Fang, Adam M Lyon, Tom C Doetschman, Patricia A Thompson, Jesse D Martinez, Jeffrey W Smith, Peter M Lance, Donato F Romagnolo
BACKGROUND: The farnesoid X receptor (FXR) regulates bile acid (BA) metabolism and possesses tumor suppressor functions. FXR expression is reduced in colorectal tumors of subjects carrying inactivated adenomatous polyposis coli (APC). Identifying the mechanisms responsible for this reduction may offer new molecular targets for colon cancer prevention. OBJECTIVE: We investigated how APC inactivation influences the regulation of FXR expression in colonic mucosal cells...
February 2016: Journal of Nutrition
Michael J Genin, Ana B Bueno, Javier Agejas Francisco, Peter R Manninen, Wayne P Bocchinfuso, Chahrzad Montrose-Rafizadeh, Ellen A Cannady, Timothy M Jones, John R Stille, Eyas Raddad, Charles Reidy, Amy Cox, M Dodson Michael, Laura F Michael
The farnesoid X receptor (FXR) is a member of the "metabolic" subfamily of nuclear receptors. Several FXR agonists have been reported in the literature to have profound effects on plasma lipids in animal models. To discover novel and effective therapies for dyslipidemia and atherosclerosis, we have developed a series of potent FXR agonists that robustly lower plasma LDL and vLDL in LDLr-/- mice. To this end the novel piperidinylisoxazole system LY2562175 was discovered. This molecule is a potent and selective FXR agonist in vitro and has robust lipid modulating properties, lowering LDL and triglycerides while raising HDL in preclinical species...
December 24, 2015: Journal of Medicinal Chemistry
Wolfgang Walther, Dennis Kobelt, Lisa Bauer, Jutta Aumann, Ulrike Stein
Multidrug resistance (MDR) is a major cause for cancer chemotherapy failure. Among the numerous strategies to overcome persistent action of proinflammatory cytokines, such as tumor necrosis factor α (TNF-α) permits downregulation of MDR-associated genes, including ATP-binding cassette, subfamily B 1 gene (ABCB1). A key regulator of ABCB1 expression is the transcription factor nuclear factor κ light chain enhancer (NF-κB)/p65. We analyzed diverging short- and long-term effects of TNF-α regarding modulation of NF-κB/p65 signaling and ABCB1 expression in colon cancer cells...
December 2015: International Journal of Oncology
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