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Epigenetics liver

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https://www.readbyqxmd.com/read/28106784/microrna-29a-alleviates-bile-duct-ligation-exacerbation-of-hepatic-fibrosis-in-mice-through-epigenetic-control-of-methyltransferases
#1
Ya-Ling Yang, Feng-Sheng Wang, Sung-Chou Li, Mao-Meng Tiao, Ying-Hsien Huang
MicroRNA-29 (miR-29) is found to modulate hepatic stellate cells' (HSCs) activation and, thereby, reduces liver fibrosis pathogenesis. Histone methyltransferase regulation of epigenetic reactions reportedly participates in hepatic fibrosis. This study is undertaken to investigate the miR-29a regulation of the methyltransferase signaling and epigenetic program in hepatic fibrosis progression. miR-29a transgenic mice (miR-29aTg mice) and wild-type littermates were subjected to bile duct-ligation (BDL) to develop cholestatic liver fibrosis...
January 18, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28105934/charm-discovery-of-combinatorial-chromatin-modification-patterns-in-hepatitis-b-virus-x-transformed-mouse-liver-cancer-using-association-rule-mining
#2
Sung Hee Park, Sun-Min Lee, Young-Joon Kim, Sangsoo Kim
BACKGROUND: Various chromatin modifications, identified in large-scale epigenomic analyses, are associated with distinct phenotypes of different cells and disease phases. To improve our understanding of these variations, many computational methods have been developed to discover novel sites and cell-specific chromatin modifications. Despite the availability of existing methods, there is still room for further improvement when they are applied to resolve the histone code hypothesis. Hence, we aim to investigate the development of a computational method to provide new insights into de novo combinatorial pattern discovery of chromatin modifications to characterize epigenetic variations in distinct phenotypes of different cells...
December 13, 2016: BMC Bioinformatics
https://www.readbyqxmd.com/read/28101838/renal-consequences-of-preterm-birth
#3
REVIEW
Amelie Stritzke, Sumesh Thomas, Harish Amin, Christoph Fusch, Abhay Lodha
BACKGROUND: The developmental origin of health and disease concept identifies the brain, cardiovascular, liver, and kidney systems as targets of fetal adverse programming with adult consequences. As the limits of viability in premature infants have been pushed to lower gestational ages, the long-term impact of prematurity on kidneys still remains a significant burden during hospital stay and beyond. OBJECTIVES: The purpose of this study is to summarize available evidence, mechanisms, and short- and long-term renal consequences of prematurity and identify nephroprotective strategies and areas of uncertainty...
December 2017: Molecular and Cellular Pediatrics
https://www.readbyqxmd.com/read/28088579/the-microrna-449-family-inhibits-tgf-%C3%AE-mediated-liver-cancer-cell-migration-by-targeting-sox4
#4
Maria Sandbothe, Reena Buurman, Nicole Reich, Luisa Greiwe, Beate Vajen, Engin Gürlevik, Vera Schäffer, Marlies Eilers, Florian Kühnel, Alejandro Vaquero, Thomas Longerich, Stephanie Roessler, Peter Schirmacher, Michael P Manns, Thomas Illig, Brigitte Schlegelberger, Britta Skawran
BACKGROUND & AIMS: Modulation of microRNA expression is considered for treatment of hepatocellular carcinoma (HCC). Therefore, we characterized the epigenetically regulated microRNA-449 family (miR-449a, miR-449b, miR-449c) with regards to its functional effects and target genes in HCC. METHODS: After transfection of miR-449a, miR-449b, and/or miR-449c, tumor-relevant functional effects were analyzed using in vitro assays and a xenograft mouse model. Binding specificities, target genes, and regulated pathways of each microRNA were identified by microarray analyses...
January 11, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28076749/epigenetic-changes-of-hepatic-glucocorticoid-receptor-in-sheep-male-offspring-undernourished-in-utero
#5
Stella Chadio, Basiliki Kotsampasi, Stylliani Taka, Emmanouil Liandris, Nikolaos Papadopoulos, Elias Plakokefalos
The aim of this study was to characterise the effects of maternal undernutrition during gestation on hepatic gluconeogenic enzyme gene expression and to determine whether such effects are mediated through epigenetic changes in the glucocorticoid receptor (GR). Pregnant ewes were fed a 50% nutrient-restricted diet from Day 0 to 30 (R1) or from Day 31 to 100 of gestation (R2) or a 100% diet throughout gestation (Control). After parturition lambs were fed to appetite. At 10 months of age offspring were euthanised and livers were removed...
January 12, 2017: Reproduction, Fertility, and Development
https://www.readbyqxmd.com/read/28071704/high-fat-diet-induced-changes-of-mouse-hepatic-transcription-and-enhancer-activity-can-be-reversed-by-subsequent-weight-loss
#6
Majken Siersbæk, Lyuba Varticovski, Shutong Yang, Songjoon Baek, Ronni Nielsen, Susanne Mandrup, Gordon L Hager, Jay H Chung, Lars Grøntved
Epigenetic factors have been suggested to play an important role in metabolic memory by trapping and maintaining initial metabolic changes within the transcriptional regulatory machinery. In this study we fed mice a high fat diet (HFD) for seven weeks followed by additional five weeks of chow, to identify HFD-mediated changes to the hepatic transcriptional program that may persist after weight loss. Mice fed a HFD displayed increased fasting insulin levels, hepatosteatosis and major changes in hepatic gene transcription associated with modulation of H3K27Ac at enhancers, but no significant changes in chromatin accessibility, indicating that HFD-regulated gene transcription is primarily controlled by modulating the activity of pre-established enhancers...
January 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28059585/initiation-of-aberrant-dna-methylation-patterns-and-heterogeneity-in-precancerous-lesions-of-human-hepatocellular-cancer
#7
Ryan A Hlady, Dan Zhou, William Puszyk, Lewis R Roberts, Chen Liu, Keith D Robertson
While intratumor heterogeneity contributes to disease progression, metastasis, and resistance to chemotherapy, it also provides a route to understanding the evolution and drivers of disease. Defects in epigenetic landscapes are intimately linked to pathogenesis of a variety of human diseases, with epigenetic deregulation promoting tumorigenesis. Understanding epigenetic heterogeneity is crucial in hepatocellular carcinoma (HCC), where epigenetic alterations are frequent, early, and pathogenic events. We determined genome-wide DNA methylation and copy number variation leveraging the Infinium 450 K in a series of regenerative nodules from within single patient livers...
January 6, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28059170/in-ovo-injection-of-betaine-alleviates-corticosterone-induced-fatty-liver-in-chickens-through-epigenetic-modifications
#8
Yun Hu, Qinwei Sun, Jie Liu, Yimin Jia, Demin Cai, Abdulrahman A Idriss, Nagmeldin A Omer, Ruqian Zhao
Betaine alleviates high-fat diet-induced fatty liver and prenatal betaine programs offspring hepatic lipid metabolism. Excessive corticosterone (CORT) exposure causes fatty liver in chickens, yet it remains unknown whether and how prenatal betaine modulates the susceptibility of CORT-induced fatty liver later in life. In this study, fertilized eggs were injected with saline or betaine before incubation, and the hatchlings were raised at 8 weeks of age followed by 7 days of subcutaneous CORT injection. CORT-induced fatty liver was less severe in betaine-treated chickens, with significantly reduced oil-red staining and hepatic triglyceride content (P < 0...
January 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28053961/iron-supplementation-reverses-the-reduction-of-hydroxymethylcytosine-in-hepatic-dna-associated-with-chronic-alcohol-consumption-in-rats
#9
Stephanie A Tammen, Jung Eun Park, Phil Kyung Shin, Simonetta Friso, Jayong Chung, Sang-Woon Choi
BACKGROUND: Alcohol is known to affect two epigenetic phenomena, DNA methylation and DNA hydroxymethylation, and iron is a cofactor of ten-eleven translocation (TET) enzymes that catalyze the conversion from methylcytosine to hydroxymethylcytosine. In the present study we aimed to determine the effects of alcohol on DNA hydroxymethylation and further effects of iron on alcohol associated epigenetic changes. METHODS: Twenty-four male Sprague-Dawley rats were fed either Lieber-DeCarli alcohol diet (36% calories from ethanol) or Lieber-DeCarli control diet along with or without iron supplementation (0...
December 2016: Journal of Cancer Prevention
https://www.readbyqxmd.com/read/28049633/progressive-epigenetic-dysregulation-in-neuroendocrine-tumour-liver-metastasis
#10
Anna Karpathakis, Harpreet Dibra, Christodoulos Pipinikas, Andrew Feber, Tiffany Morris, Joshua M Francis, Dahmane Oukrif, Dalvinder Mandair, Marinos Pericleous, Mullan Mohmaduvesh, Stefano Serra, Olagunju Ogunbiyi, Marco Novelli, Tu Vinh Luong, Sylvia L Asa, Matthew H Kulke, Christos Toumpanakis, Tim Meyer, Martyn Caplin, Stephan Beck, Christina Thirlwell
Dear Editor The incidence of small intestinal neuroendocrine tumours (SINETs) is increasing and distant metastases are present at diagnosis in 70% of cases, the liver being the most common site of metastasis. Despite this, our understanding of the mechanisms underlying metastatic progression of SINETs is currently limited and prior studies of the molecular biology of SINET liver metastases (LM) have been performed predominantly in small cohorts utilising candidate based techniques.
January 3, 2017: Endocrine-related Cancer
https://www.readbyqxmd.com/read/28039067/prenatal-betaine-exposure-alleviates-corticosterone-induced-inhibition-of-cyp27a1-expression-in-the-liver-of-juvenile-chickens-associated-with-its-promoter-dna-methylation
#11
Yun Hu, Qinwei Sun, Yibo Zong, Jie Liu, Abdulrahman A Idriss, Nagmeldin A Omer, Ruqian Zhao
Sterol 27-hydroxylase (CYP27A1) plays an important role in cholesterol homeostasis by degrading cholesterol to bile acids. Betaine can alleviate high-fat diet-induced hepatic cholesterol accumulation and maternal betaine treatment programs the hepatic expression of CYP27A1 in offspring. Excessive corticosterone (CORT) exposure causes hepatic cholesterol deposition in chickens, yet it remains unknown whether prenatal betaine modulates CORT-induced cholesterol accumulation in chicken liver later in life and whether it involves epigenetic gene regulation of CYP27A1...
December 27, 2016: General and Comparative Endocrinology
https://www.readbyqxmd.com/read/28038456/dna-methylation-landscape-of-hepatoblastomas-reveals-arrest-at-early-stages-of-liver-differentiation-and-cancer-related-alterations
#12
Mariana Maschietto, Tatiane Cristina Rodrigues, André Yoshiaki Kashiwabara, Érica Sara Souza de Araujo, Talita Ferreira Marques Aguiar, Cecilia Maria Lima da Costa, Isabela Werneck da Cunha, Luciana Dos Reis Vasques, Monica Cypriano, Helena Brentani, Silvia Regina Caminada de Toledo, Peter Lees Pearson, Dirce Maria Carraro, Carla Rosenberg, Ana Cristina Victorino Krepischi
Hepatoblastomas are uncommon embryonal liver tumors accounting for approximately 80% of childhood hepatic cancer. We hypothesized that epigenetic changes, including DNA methylation, could be relevant to hepatoblastoma onset. The methylomes of eight matched hepatoblastomas and non-tumoral liver tissues were characterized, and data were validated in an independent group (11 hepatoblastomas). In comparison to differentiated livers, hepatoblastomas exhibited a widespread and non-stochastic pattern of global low-level hypomethylation...
December 25, 2016: Oncotarget
https://www.readbyqxmd.com/read/28036298/clinical-and-biological-significance-of-mir-23b-and-mir-193a-in-human-hepatocellular-carcinoma
#13
Ilaria Grossi, Bruna Arici, Nazario Portolani, Giuseppina De Petro, Alessandro Salvi
Hepatocellular carcinoma (HCC) is the most common cancer of the liver with a very poor prognosis. The dysregulation of microRNAs (miRs) is indeed implicated in HCC onset and progression. In this study, we have evaluated the expression of miR-23b and miR-193a in a large cohort of 59 and 67 HCC patients, respectively. miR-23b and miR-193a resulted significantly down-regulated in primary HCCs compared to their matched peritumoral counterparts. Furthermore, patients with higher miR-193a expression exhibited longer OS and DFS, suggesting that miR-193a may be a molecular prognostic factor for HCC patients...
December 28, 2016: Oncotarget
https://www.readbyqxmd.com/read/28030845/withdrawn-could-some-epigenetic-modifications-hold-the-key-to-opposing-the-metabolic-syndrome
#14
REVIEW
Giovanni Tarantino, Matteo Nicola Di Minno, Carmine Finelli
Ahead of Print article withdrawn by publisher.
December 21, 2016: Oncotarget
https://www.readbyqxmd.com/read/28030474/therapeutic-benefits-of-the-methyl-donor-s-adenosylmethionine-sam-on-nerve-injury-induced-mechanical-hypersensitivity-and-cognitive-impairment-in-mice
#15
Stéphanie Grégoire, Magali Millecamps, Lina Naso, Sonia Do Carmo, A Claudio Cuello, Moshe Szyf, Laura S Stone
Despite considerable advances in understanding mechanisms involved in chronic pain, effective treatment remains elusive. Co-morbid conditions including anxiety, depression and cognitive impairment further impact quality of life. Chronic pain is associated with reversible changes in brain anatomy and function and with long-term changes in gene expression. Epigenetic mechanisms, including DNA methylation, contribute to wide-spread and long-lasting reprogramming of gene expression. We previously reported decreases in global DNA methylation in the mouse frontal cortex six months following induction of neuropathic pain using the Spared Nerve Injury (SNI) model...
December 22, 2016: Pain
https://www.readbyqxmd.com/read/28025657/mir-200a-controls-hepatic-stellate-cell-activation-and-fibrosis-via-sirt1-notch1-signal-pathway
#16
Jing-Jing Yang, Hui Tao, Li-Ping Liu, Wei Hu, Zi-Yu Deng, Jun Li
OBJECTIVES: miR-200a has been established as a key regulator of HSC activation processes in liver fibrosis. Epigenetic silencing of miR-200a contributing to SIRT1 over-expression has been discussed in breast cancer; however, whether miR-200a controls SIRT1 gene expression in hepatic fibrosis is still unknown. METHODS AND MATERIALS: We analyzed miR-200a regulation of SIRT1 expression in CCl4-induced liver fibrosis and TGF-β1-mediated activation of HSC. miR-200a, SIRT1, α-SMA, Col1A1, Notch1 and NICD expression were estimated by Western blotting, qRT-PCR and Immunohistochemistry...
December 26, 2016: Inflammation Research: Official Journal of the European Histamine Research Society ... [et Al.]
https://www.readbyqxmd.com/read/28013212/organ-specific-epigenetic-changes-induced-by-the-non-genotoxic-liver-carcinogen-methapyrilene-in-fischer-344-rats
#17
Svitlana Shpyleva, Kostiantyn Dreval, Aline de Conti, Iryna Kindrat, Stepan Melnyk, Jian Yan, Tao Chen, Frederick A Beland, Igor P Pogribny
Continuous lifetime exposure to certain natural and man-made chemicals is a major cause of cancers in humans; therefore, evaluating the carcinogenic risks of chemicals remains important. Currently, substantial progress has been made in identification of genotoxic carcinogens; in contrast, predicting a carcinogenic potential of non-genotoxic compounds is a challenge due to many different modes of action that may lead to tumorigenesis. In the present study, we investigated the effects of the non-genotoxic liver carcinogen methapyrilene and the nongenotoxic non-carcinogen usnic acid at doses that do not exhibit organ cytotoxicity on epigenomic alterations in the liver and kidneys of Fischer 344 (F344) rats...
December 24, 2016: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28006867/differential-profile-of-activated-regulatory-t-cell-subsets-and-micrornas-in-tolerant-liver-transplant-recipients
#18
B Revilla-Nuin, A de Bejar, L Martínez-Alarcón, J I Herrero, C M Martínez-Cáceres, P Ramírez, A Baroja-Mazo, J A Pons
: Regulatory T cells (Tregs) play a potential role in operational tolerance in liver transplant patients, and microRNAs (miRNAs) are known to be involved in immunological responses and tolerance. Thus, we analyzed the implication of different peripheral blood Treg subsets and miRNAs on liver transplantation tolerance in 24 tolerant (Tol) and 23 non-tolerant (non-Tol) liver transplant recipients by cellular, genetic and epigenetic approximation. Non-Tol patients had a lower demethylation rate of the FOXP3 Treg-specific demethylated region (TSDR) than Tol patients that correlated with the frequency of circulating Tregs...
December 22, 2016: Liver Transplantation
https://www.readbyqxmd.com/read/27993651/nafld-is-associated-with-methylation-shifts-with-relevance-for-the-expression-of-genes-involved-in-lipoprotein-particle-composition
#19
Jessica Mwinyi, Adrian E Boström, Claudia Pisanu, Susan K Murphy, Wiebke Erhart, Clemens Schafmayer, Jochen Hampe, Cynthia Moylan, Helgi B Schiöth
Non-alcoholic fatty liver disease (NAFLD) is characterized by the accumulation of triglycerides, cholesterol and toxic free fatty acids and is related to low vitamin D levels. In an analysis of specific gene sets we elucidate to what extent NAFLD associates to epigenetic and related transcriptional changes in gene networks regulating lipid, energy and vitamin D balance. Two gene clusters responsible for lipid homeostasis (74 genes) and vitamin D and energy balance (31 genes) were investigated with regard to average epigenetic shifts within the first 1500bp next to the transcriptional start site...
December 18, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27990121/targeting-mechanotransduction-at-the-transcriptional-level-yap-and-brd4-are-novel-therapeutic-targets-for-the-reversal-of-liver-fibrosis
#20
REVIEW
Altynbek Zhubanchaliyev, Aibar Temirbekuly, Kuralay Kongrtay, Leah C Wanshura, Jeannette Kunz
Liver fibrosis is the result of a deregulated wound healing process characterized by the excessive deposition of extracellular matrix. Hepatic stellate cells (HSCs), which are activated in response to liver injury, are the major source of extracellular matrix and drive the wound healing process. However, chronic liver damage leads to perpetual HSC activation, progressive formation of pathological scar tissue and ultimately, cirrhosis and organ failure. HSC activation is triggered largely in response to mechanosignaling from the microenvironment, which induces a profibrotic nuclear transcription program that promotes HSC proliferation and extracellular matrix secretion thereby setting up a positive feedback loop leading to matrix stiffening and self-sustained, pathological, HSC activation...
2016: Frontiers in Pharmacology
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