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HNF4α

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https://www.readbyqxmd.com/read/27909409/3-5-3-triiodo-l-thyronine-and-3-5-diiodo-l-thyronine-affected-metabolic-pathways-in-liver-of-ldl-receptor-deficient-mice
#1
Maria Moreno, Elena Silvestri, Maria Coppola, Ira J Goldberg, Li-Shin Huang, Anna M Salzano, Fulvio D'Angelo, Joel R Ehrenkranz, Fernando Goglia
3,5,3'-triiodo-L-thyronine (T3) and 3,5-diiodo-L-thyronine (T2), when administered to a model of familial hypercholesterolemia, i.e., low density lipoprotein receptor (LDLr)-knockout (Ldlr(-/-)) mice fed with a Western type diet (WTD), dramatically reduce circulating total and very low-density lipoprotein/LDL cholesterol with decreased liver apolipoprotein B (ApoB) production. The aim of the study was to highlight putative molecular mechanisms to manage cholesterol levels in the absence of LDLr. A comprehensive comparative profiling of changes in expression of soluble proteins in livers from Ldlr(-/-) mice treated with either T3 or T2 was performed...
2016: Frontiers in Physiology
https://www.readbyqxmd.com/read/27903283/systematic-analysis-of-chromatin-interactions-at-disease-associated-loci-links-novel-candidate-genes-to-inflammatory-bowel-disease
#2
Claartje A Meddens, Magdalena Harakalova, Noortje A M van den Dungen, Hassan Foroughi Asl, Hemme J Hijma, Edwin P J G Cuppen, Johan L M Björkegren, Folkert W Asselbergs, Edward E S Nieuwenhuis, Michal Mokry
BACKGROUND: Genome-wide association studies (GWAS) have revealed many susceptibility loci for complex genetic diseases. For most loci, the causal genes have not been identified. Currently, the identification of candidate genes is predominantly based on genes that localize close to or within identified loci. We have recently shown that 92 of the 163 inflammatory bowel disease (IBD)-loci co-localize with non-coding DNA regulatory elements (DREs). Mutations in DREs can contribute to IBD pathogenesis through dysregulation of gene expression...
November 30, 2016: Genome Biology
https://www.readbyqxmd.com/read/27878730/mesenchymal-epithelial-transition-in-culture-of-stromal-progenitor-cells-isolated-from-the-liver-of-a-patient-with-alcoholic-cirrhosis
#3
I V Kholodenko, R V Kholodenko, G V Manukyan, V V Burunova, K N Yarygin
The cells isolated from biopsy specimen of a patient with alcoholic liver cirrhosis and cultured under standard conditions for obtaining stromal cell culture clearly diverged during early passages into two morphologically and phenotypically different subtypes: epithelial and mesenchymal. Mesenchymal cells expressed CD90 and CD44 and epithelial cells expressed CD166, CD227, and hepatocyte growth factor receptor Met. Starting from passage 6, the culture underwent spontaneous morphological changes and by passages 8-10 contained only epithelium-like cells...
November 23, 2016: Bulletin of Experimental Biology and Medicine
https://www.readbyqxmd.com/read/27875772/hnf4%C3%AE-is-a-key-gene-that-can-generate-columnar-metaplasia-in-oesophageal-epithelium
#4
Benjamin J Colleypriest, Zoë D Burke, Leonard P Griffiths, Yu Chen, Wei-Yuan Yu, Ramiro Jover, Michael Bock, Leigh Biddlestone, Jonathan M Quinlan, Stephen G Ward, J Mark Farrant, Jonathan M W Slack, David Tosh
Barrett's metaplasia is the only known morphological precursor to oesophageal adenocarcinoma and is characterized by replacement of stratified squamous epithelium by columnar epithelium. The cell of origin is uncertain and the molecular mechanisms responsible for the change in cellular phenotype are poorly understood. We therefore explored the role of two transcription factors, Cdx2 and HNF4α in the conversion using primary organ cultures. Biopsy samples from cases of human Barrett's metaplasia were analysed for the presence of CDX2 and HNF4α...
November 19, 2016: Differentiation; Research in Biological Diversity
https://www.readbyqxmd.com/read/27809333/yap-tead-and-hnf4%C3%AE-repress-reciprocally-to-regulate-hepatocarcinogenesis
#5
Wang-Yu Cai, Ling-Yun Lin, Han Hao, Sai-Man Zhang, Fei Ma, Xin-Xin Hong, Hui Zhang, Qing-Feng Liu, Guo-Dong Ye, Guang-Bin Sun, Yun-Jia Liu, Sheng-Nan Li, Yuan-Yuan Xie, Jian-Chun Cai, Li Bo-An
: Great progress has been achieved in the study of Hippo signaling in regulating tumorigenesis; however, the downstream molecular events that mediate this process have not been completely defined. Moreover, the regulation of Hippo signaling during tumorigenesis in hepatocellular carcinoma (HCC) remains largely unknown. In the present study, we systematically investigated the relationship between YAP-TEAD and HNF4α in the hepatocarcinogenesis of HCC cells. Our results indicated that HNF4α expression was negatively regulated by YAP1 in HCC cells via a ubiquitin proteasome pathway...
November 3, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/27752141/diabetes-linked-transcription-factor-hnf4%C3%AE-regulates-metabolism-of-endogenous-methylarginines-and-%C3%AE-aminoisobutyric-acid-by-controlling-expression-of-alanine-glyoxylate-aminotransferase-2
#6
Dmitry V Burdin, Alexey A Kolobov, Chad Brocker, Alexey A Soshnev, Nikolay Samusik, Anton V Demyanov, Silke Brilloff, Natalia Jarzebska, Jens Martens-Lobenhoffer, Maren Mieth, Renke Maas, Stefan R Bornstein, Stefanie M Bode-Böger, Frank Gonzalez, Norbert Weiss, Roman N Rodionov
Elevated levels of circulating asymmetric and symmetric dimethylarginines (ADMA and SDMA) predict and potentially contribute to end organ damage in cardiovascular diseases. Alanine-glyoxylate aminotransferase 2 (AGXT2) regulates systemic levels of ADMA and SDMA, and also of beta-aminoisobutyric acid (BAIB)-a modulator of lipid metabolism. We identified a putative binding site for hepatic nuclear factor 4 α (HNF4α) in AGXT2 promoter sequence. In a luciferase reporter assay we found a 75% decrease in activity of Agxt2 core promoter after disruption of the HNF4α binding site...
October 18, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27723751/nuclear-receptors-control-pro-viral-and-antiviral-metabolic-responses-to-hepatitis-c-virus-infection
#7
Gahl Levy, Naomi Habib, Maria Angela Guzzardi, Daniel Kitsberg, David Bomze, Elishai Ezra, Basak E Uygun, Korkut Uygun, Martin Trippler, Joerg F Schlaak, Oren Shibolet, Ella H Sklan, Merav Cohen, Joerg Timm, Nir Friedman, Yaakov Nahmias
Viruses lack the basic machinery needed to replicate and therefore must hijack the host's metabolism to propagate. Virus-induced metabolic changes have yet to be systematically studied in the context of host transcriptional regulation, and such studies shoul offer insight into host-pathogen metabolic interplay. In this work we identified hepatitis C virus (HCV)-responsive regulators by coupling system-wide metabolic-flux analysis with targeted perturbation of nuclear receptors in primary human hepatocytes. We found HCV-induced upregulation of glycolysis, ketogenesis and drug metabolism, with glycolysis controlled by activation of HNF4α, ketogenesis by PPARα and FXR, and drug metabolism by PXR...
October 10, 2016: Nature Chemical Biology
https://www.readbyqxmd.com/read/27709008/crosstalk-of-hnf4%C3%AE-with-extracellular-and-intracellular-signaling-pathways-in-the-regulation-of-hepatic-metabolism-of-drugs-and-lipids
#8
Hong Lu
The liver is essential for survival due to its critical role in the regulation of metabolic homeostasis. Metabolism of xenobiotics, such as environmental chemicals and drugs by the liver protects us from toxic effects of these xenobiotics, whereas metabolism of cholesterol, bile acids (BAs), lipids, and glucose provide key building blocks and nutrients to promote the growth or maintain the survival of the organism. As a well-established master regulator of liver development and function, hepatocyte nuclear factor 4 alpha (HNF4α) plays a critical role in regulating a large number of key genes essential for the metabolism of xenobiotics, metabolic wastes, and nutrients...
September 2016: Acta Pharmaceutica Sinica. B
https://www.readbyqxmd.com/read/27677335/epigenomic-profiling-of-primary-gastric-adenocarcinoma-reveals-super-enhancer-heterogeneity
#9
Wen Fong Ooi, Manjie Xing, Chang Xu, Xiaosai Yao, Muhammad Khairul Ramlee, Mei Chee Lim, Fan Cao, Kevin Lim, Deepak Babu, Lai-Fong Poon, Joyce Lin Suling, Aditi Qamra, Astrid Irwanto, James Qu Zhengzhong, Tannistha Nandi, Ai Ping Lee-Lim, Yang Sun Chan, Su Ting Tay, Ming Hui Lee, James O J Davies, Wai Keong Wong, Khee Chee Soo, Weng Hoong Chan, Hock Soo Ong, Pierce Chow, Chow Yin Wong, Sun Young Rha, Jianjun Liu, Axel M Hillmer, Jim R Hughes, Steve Rozen, Bin Tean Teh, Melissa Jane Fullwood, Shang Li, Patrick Tan
Regulatory enhancer elements in solid tumours remain poorly characterized. Here we apply micro-scale chromatin profiling to survey the distal enhancer landscape of primary gastric adenocarcinoma (GC), a leading cause of global cancer mortality. Integrating 110 epigenomic profiles from primary GCs, normal gastric tissues and cell lines, we highlight 36,973 predicted enhancers and 3,759 predicted super-enhancers respectively. Cell-line-defined super-enhancers can be subclassified by their somatic alteration status into somatic gain, loss and unaltered categories, each displaying distinct epigenetic, transcriptional and pathway enrichments...
September 28, 2016: Nature Communications
https://www.readbyqxmd.com/read/27660075/hnf-4alpha-negatively-regulates-hepcidin-expression-through-bmpr1a-in-hepg2-cells
#10
Wencai Shi, Heyang Wang, Xuan Zheng, Xin Jiang, Zheng Xu, Hui Shen, Min Li
Hepcidin synthesis is reported to be inadequate according to the body iron store in patients with non-alcoholic fatty liver disease (NAFLD) undergoing hepatic iron overload (HIO). However, the underlying mechanisms remain unclear. We hypothesize that hepatocyte nuclear factor-4α (HNF-4α) may negatively regulate hepcidin expression and contribute to hepcidin deficiency in NAFLD patients. The effect of HNF-4α on hepcidin expression was observed by transfecting specific HNF-4α small interfering RNA (siRNA) or plasmids into HepG2 cells...
September 23, 2016: Biological Trace Element Research
https://www.readbyqxmd.com/read/27659712/clinical-and-molecular-characterization-of-a-novel-ins-mutation-identified-in-patients-with-mody-phenotype
#11
Barbara Piccini, Rosangela Artuso, Lorenzo Lenzi, Monica Guasti, Giulia Braccesi, Federica Barni, Emilio Casalini, Sabrina Giglio, Sonia Toni
Correct diagnosis of Maturity-Onset Diabetes of the Young (MODY) is based on genetic tests requiring an appropriate subject selection by clinicians. Mutations in the insulin (INS) gene rarely occur in patients with MODY. This study is aimed at determining the genetic background and clinical phenotype in patients with suspected MODY. 34 patients with suspected MODY, negative for mutations in the GCK, HNF1α, HNF4α, HNF1β and PDX1 genes, were screened by next generation sequencing (NGS). A heterozygous INS mutation was identified in 4 members of the same family...
September 19, 2016: European Journal of Medical Genetics
https://www.readbyqxmd.com/read/27610747/specific-oct1-and-abcg2-polymorphisms-are-associated-with-lamotrigine-concentrations-in-chinese-patients-with-epilepsy
#12
Chun-Hong Shen, Yin-Xi Zhang, Ru-Yi Lu, Bo Jin, Shan Wang, Zhi-Rong Liu, Ye-Lei Tang, Mei-Ping Ding
PURPOSE: The pharmacokinetics of Lamotrigine (LTG) varies widely among patients with epilepsy. In this study, we are aiming to investigate the effects of OCT1, ABCG2, ABCC2 and HNF4α genetic polymorphisms on plasma LTG concentrations and therapeutic efficacy in Chinese patients with epilepsy. METHODS: The study cohort comprised 112 Han Chinese patients with epilepsy who were receiving LTG monotherapy. Blood samples were taken and LTG levels were measured. The polymorphisms of OCT1 rs2282143, rs628031, ABCG2 rs2231142, rs2231137, ABCC2 rs2273697 and HNF4α rs2071197, rs3212183 were determined...
September 1, 2016: Epilepsy Research
https://www.readbyqxmd.com/read/27583872/dna-methylations-of-mc4r-and-hnf4%C3%AE-are-associated-with-increased-triglyceride-levels-in-cord-blood-of-preterm-infants
#13
Eun Jin Kwon, Hye Ah Lee, Young-Ah You, Hyesook Park, Su Jin Cho, Eun Hee Ha, Young Ju Kim
The association of preterm birth with obesity and metabolic syndrome later in life is well established. Although the biological mechanism for this association is poorly understood, epigenetic alterations of metabolic-related genes in early life may have important roles in metabolic dysfunction. Thus, we investigated the associations of DNA methylations of melanocortin 4 receptor (MC4R) and hepatocyte nuclear factor 4 alpha (HNF4α) with metabolic profiles in cord blood of term and preterm infants.We measured metabolic profiles in cord blood samples of 85 term and 85 preterm infants...
August 2016: Medicine (Baltimore)
https://www.readbyqxmd.com/read/27542413/hepatic-loss-of-borealin-impairs-postnatal-liver-development-regeneration-and-hepatocarcinogenesis
#14
Lu Li, Dan Li, Feng Tian, Jin Cen, Xiaotao Chen, Yuan Ji, Lijian Hui
Borealin, a member of the chromosomal passenger complex, plays a key regulatory role at centromeres and the central spindle during mitosis. Loss of Borealin leads to defective cell proliferation and early embryonic lethality. The in vivo functions of Borealin in mammalian postnatal development, tissue homeostasis, and tumorigenesis remain elusive. We specifically analyzed the role of Borealin in regulating postnatal liver development, damage-induced liver regeneration, and liver carcinogenesis using mice carrying conditional Borealin alleles...
September 30, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27501760/direct-induction-of-hepatocyte-like-cells-from-immortalized-human-bone-marrow-mesenchymal-stem-cells-by-overexpression-of-hnf4%C3%AE
#15
Xiaojun Hu, Peiyi Xie, Weiqiang Li, Zhengran Li, Hong Shan
Hepatocytes from human bone marrow-derived mesenchymal stem cells (hBM-MSCs) are expected to be a useful source for cell transplantation. However, relatively low efficiency and repeatability of hepatic differentiation of human BM-MSCs remains an obstacle for clinical translation. Hepatocyte nuclear factor 4 alpha (HNF4α), a critical transcription factor, plays an essential role in the entire process of liver development. In this study, immortalized hBM-MSCs, UE7T-13 cells were transduced with a lentiviral vector containing HNF4α...
September 16, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27477312/hepatitis-c-virus-suppresses-hepatocyte-nuclear-factor-4-alpha-a-key-regulator-of-hepatocellular-carcinoma
#16
Ioanna Vallianou, Dimitra Dafou, Niki Vassilaki, Penelope Mavromara, Margarita Hadzopoulou-Cladaras
Hepatitis C Virus (HCV) infection presents with a disturbed lipid profile and can evolve to hepatic steatosis and hepatocellular carcinoma (HCC). Hepatocyte Nuclear Factor 4 alpha (HNF4α) is the most abundant transcription factor in the liver, a key regulator of hepatic lipid metabolism and a critical determinant of Epithelial to Mesenchymal Transition and hepatic development. We have previously shown that transient inhibition of HNF4α initiates transformation of immortalized hepatocytes through a feedback loop consisting of miR-24, IL6 receptor (IL6R), STAT3, miR-124 and miR-629, suggesting a central role of HNF4α in HCC...
September 2016: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/27474396/iterative-use-of-nuclear-receptor-nr5a2-regulates-multiple-stages-of-liver-and-pancreas-development
#17
Sahar Nissim, Olivia Weeks, Jared C Talbot, John W Hedgepeth, Julia Wucherpfennig, Stephanie Schatzman-Bone, Ian Swinburne, Mauricio Cortes, Kristen Alexa, Sean Megason, Trista E North, Sharon L Amacher, Wolfram Goessling
The stepwise progression of common endoderm progenitors into differentiated liver and pancreas organs is regulated by a dynamic array of signals that are not well understood. The nuclear receptor subfamily 5, group A, member 2 gene nr5a2, also known as Liver receptor homolog-1 (Lrh-1) is expressed in several tissues including the developing liver and pancreas. Here, we interrogate the role of Nr5a2 at multiple developmental stages using genetic and chemical approaches and uncover novel pleiotropic requirements during zebrafish liver and pancreas development...
October 1, 2016: Developmental Biology
https://www.readbyqxmd.com/read/27472219/hepatocyte-nuclear-factor-4%C3%AE-hnf4%C3%AE-is-a-transcription-factor-of-vertebrate-fatty-acyl-desaturase-gene-as-identified-in-marine-teleost-siganus-canaliculatus
#18
Yewei Dong, Shuqi Wang, Junliang Chen, Qinghao Zhang, Yang Liu, Cuihong You, Óscar Monroig, Douglas R Tocher, Yuanyou Li
Rabbitfish Siganus canaliculatus was the first marine teleost demonstrated to have the capability of biosynthesizing long-chain polyunsaturated fatty acids (LC-PUFA) from C18 precursors, and to possess a Δ4 fatty acyl desaturase (Δ4 Fad) which was the first report in vertebrates, and is a good model for studying the regulatory mechanisms of LC-PUFA biosynthesis in teleosts. In order to understand regulatory mechanisms of transcription of Δ4 Fad, the gene promoter was cloned and characterized in the present study...
2016: PloS One
https://www.readbyqxmd.com/read/27466601/ppar%C3%AE-downregulates-hepatic-glutaminase-expression-in-mice-fed-diets-with-different-protein-carbohydrate-ratios
#19
Laura A Velázquez-Villegas, Tania Charabati, Alejandra V Contreras, Gabriela Alemán, Nimbe Torres, Armando R Tovar
BACKGROUND: Glutamine is catabolized in the liver by glutaminase 2 (GLS2). Evidence suggests that peroxisome proliferator-activated receptor α (PPARα) represses the expression of several amino acid-catabolizing enzymes, but for Gls2 this is unknown. OBJECTIVE: The aim of the study was to assess whether PPARα regulates Gls2 expression. METHODS: For 8 d, 7-9-wk-old male C57BL/6 wild-type (WT) and Ppara-null mice weighing 23.4 ± 0.5 g were fed diets with different dietary protein:carbohydrate (DP:DCH) ratios (6%:77%, 20%:63%, or 50%:33%)...
September 2016: Journal of Nutrition
https://www.readbyqxmd.com/read/27402843/%C3%AE-apo-10-carotenoids-modulate-placental-microsomal-triglyceride-transfer-protein-expression-and-function-to-optimize-transport-of-intact-%C3%AE-carotene-to-the-embryo
#20
Brianna K Costabile, Youn-Kyung Kim, Jahangir Iqbal, Michael V Zuccaro, Lesley Wassef, Sureshbabu Narayanasamy, Robert W Curley, Earl H Harrison, M Mahmood Hussain, Loredana Quadro
β-Carotene is an important source of vitamin A for the mammalian embryo, which depends on its adequate supply to achieve proper organogenesis. In mammalian tissues, β-carotene 15,15'-oxygenase (BCO1) converts β-carotene to retinaldehyde, which is then oxidized to retinoic acid, the biologically active form of vitamin A that acts as a transcription factor ligand to regulate gene expression. β-Carotene can also be cleaved by β-carotene 9',10'-oxygenase (BCO2) to form β-apo-10'-carotenal, a precursor of retinoic acid and a transcriptional regulator per se The mammalian embryo obtains β-carotene from the maternal circulation...
August 26, 2016: Journal of Biological Chemistry
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