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https://www.readbyqxmd.com/read/28536011/tg737-regulates-epithelial-mesenchymal-transition-and-cancer-stem%C3%A2-cell-properties-via-a-negative-feedback-circuit-between-snail-and%C3%A2-hnf4%C3%AE-during-liver-stem-cell-malignant-transformation
#1
Qike Huang, Meng Pu, Ge Zhao, Bin Dai, Zhenyuan Bian, Haili Tang, Chong Chen, Wei Liu, Xuan Qu, Liangliang Shen, Kaishan Tao
Determining the origin of liver cancer stem cells is important for treating hepatocellular carcinoma. Tg737 deficiency plays an important role in the malignant transformation of liver stem cells, but the underlying mechanism remains unclear. Here we established a chemical-induced mouse hepatoma model and found that Tg737 and hepatocyte nuclear factor 4-alpha (HNF4α) expression decreased and epithelial-mesenchymal transition (EMT)-related marker expression increased during liver cancer development. To investigate the underlying mechanism, we knocked down Tg737 in WB-F344 (WB) rat hepatic oval cells...
May 20, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28535186/fxr-gankyrin-axis-is-involved-in-development-of-pediatric-liver-cancer
#2
Leila Valanejad, Kyle Lewis, Mary Wright, Yanjun Jiang, Amber D'Souza, Rebekah Karns, Rachel Sheridan, Anita Gupta, Kevin Bove, David Witte, James Geller, Gregory Tiao, David L Nelson, Lubov Timchenko, Nikolai Timchenko
The development of hepatoblastoma (HBL) is associated with failure of hepatic stem cells (HSC) to differentiate into hepatocytes. Despite intensive investigations, mechanisms of the failure of HSC to differentiate are not known. We found that oncogene Gankyrin (Gank) is involved in the inhibition of differentiation of HSC via triggering degradation of tumor suppressor proteins (TSPs) Rb, p53, C/EBPα and HNF4α. Our data show that the activation of a repressor of Gank, farnesoid X receptor, FXR, after initiation of liver cancer by Diethylnitrosamine (DEN) prevents the development of liver cancer by inhibiting Gank and rescuing tumor suppressor proteins...
May 23, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/28504115/protocatechuic-acid-inhibits-hepatitis-b-virus-replication-by-activating-erk1-2-pathway-and-down-regulating-hnf4%C3%AE-and-hnf1%C3%AE-in-vitro
#3
Xiao-Qing Dai, Wen-Tao Cai, Xiao Wu, Yong Chen, Feng-Mei Han
AIMS: Protocatechuic acid (PCA) is a phenolic compound found in many antiviral Chinese herbal medicines. HNF4α and HNF1α, the members of hepatocyte nuclear factor (HNF) family, play an important regulatory role in the gene transcription of hepatitis B virus (HBV). Previous studies found that PCA inhibited HBV antigen secretion and HBV DNA replication in HepG2.2.15 cells, but its anti-HBV mechanism has not been fully understood. We aim to illustrate the anti-HBV mechanism of PCA. MATERIALS AND METHODS: MTT was used to estimate cytotoxicity...
May 12, 2017: Life Sciences
https://www.readbyqxmd.com/read/28499695/dapagliflozin-modulates-glucagon-secretion-in-an-sglt2-independent-manner-in-murine-alpha-cells
#4
A Solini, G Sebastiani, L Nigi, E Santini, C Rossi, F Dotta
AIM: SGLT2 inhibitors reduce renal glucose uptake through an insulin-independent mechanism. They also increase glucagon concentration, although the extent to which this is due to a direct effect on pancreatic alpha cells remains unclear. METHODS: In the present work, αTC1 cells treated with the SGLT2 inhibitor dapagliflozin (Dapa) were analyzed for glucose transporters, molecular mediators of hormone secretion, glucagon and GLP-1 release, and the effects of somatostatin...
May 9, 2017: Diabetes & Metabolism
https://www.readbyqxmd.com/read/28498421/molecular-analysis-of-the-mouse-brain-exposed-to-chronic-mild-stress-the-influence-of-hepatocyte-nuclear-factor-4%C3%AE-on-physiological-homeostasis
#5
Kaoru Ikubo, Kyosuke Yamanishi, Nobutaka Doe, Takuya Hashimoto, Miho Sumida, Yuko Watanabe, Yosif El-Darawish, Wen Li, Haruki Okamura, Hiromichi Yamanishi, Hisato Matsunaga
Major depressive disorder (MDD) is a prevalent disorder that causes considerable disability in social functioning and is a risk factor for physical diseases. Recent clinical reports have demonstrated a marked association between MDD and physiological dyshomeostasis induced by metabolic disorders, including diabetes, hormone abnormalities and autoimmune diseases. The authors of the present study have previously analyzed comparative gene expression profiles in the prefrontal cortex (PFC) of a chronic mild stress (CMS) animal model of MDD...
May 11, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28488786/gadoxetic-acid-enhanced-magnetic-resonance-imaging-reflects-co-activation-of-%C3%AE-catenin-and-hepatocyte-nuclear-factor-4%C3%AE-in-hepatocellular-carcinoma
#6
Azusa Kitao, Osamu Matsui, Norihide Yoneda, Kazuto Kozaka, Satoshi Kobayashi, Wataru Koda, Tetsuya Minami, Dai Inoue, Kotaro Yoshida, Taro Yamashita, Tatsuya Yamashita, Shuichi Kaneko, Hiroyuki Takamura, Tetsuo Ohta, Hiroko Ikeda, Yasunori Sato, Yasuni Nakanuma, Kenichi Harada, Ryuichi Kita, Toshifumi Gabata
AIM: The aim of this study is to clarify the correlation of the co-activation of β-catenin and hepatocyte nuclear factor (HNF) 4α with the findings of gadoxetic acid enhanced MRI, organic anion transporting polypeptide (OATP) 1B3 expression and histological differentiation grade in hepatocellular carcinoma (HCC). METHODS: Surgically resected 196 HCC in 174 patients were enrolled in this study. HCC were classified into four groups by immunohistochemical expression of β-catenin, glutamine synthetase (GS) and HNF4α: β-catenin/GS (positive: +) HNF4α (+), β-catenin/GS (+) HNF4α (negative: -), β-catenin/GS (-) HNF4α (+) and β-catenin/GS (-) HNF4α (-)...
May 10, 2017: Hepatology Research: the Official Journal of the Japan Society of Hepatology
https://www.readbyqxmd.com/read/28475422/the-flavonoid-derivative-4-nitro-6-hydroxyflavone-suppresses-the-activity-of-hnf4%C3%AE-and-stimulates-the-degradation-of-hnf4%C3%AE-protein-through-the-activation-of-ampk
#7
Jun Inoue, Shiori Ikeda, Tomohiko Kanayama, Ryuichiro Sato
Hepatocyte nuclear factor 4α (HNF4α) is a nuclear receptor that regulates the expression of genes involved in a number of critical metabolic pathways. The modulation of HNF4α activity is thought to be a promising drug target pathway for hyperlipidemia. To identify compounds that reduce the activity of HNF4α, we conducted luciferase reporter assays using the promoter region of microsomal triglyceride transfer protein (MTP) gene, which contains an HNF4α-responsive element. Using this system, we show here that the flavonoid derivative 4'-nitro-6-hydroxyflavone (NOHF) suppresses MTP promoter activity...
May 5, 2017: Bioscience, Biotechnology, and Biochemistry
https://www.readbyqxmd.com/read/28470937/endothelial-cell-derived-matrix-promotes-the-metabolic-functional-maturation-of-hepatocyte-via-integrin-src-signalling
#8
Xinyue Guo, Weihong Li, Minghui Ma, Xin Lu, Haiyan Zhang
The extracellular matrix (ECM) microenvironment is involved in the regulation of hepatocyte phenotype and function. Recently, the cell-derived extracellular matrix has been proposed to represent the bioactive and biocompatible materials of the native ECM. Here, we show that the endothelial cell-derived matrix (EC matrix) promotes the metabolic maturation of human adipose stem cell-derived hepatocyte-like cells (hASC-HLCs) through the activation of the transcription factor forkhead box protein A2 (FOXA2) and the nuclear receptors hepatocyte nuclear factor 4 alpha (HNF4α) and pregnane X receptor (PXR)...
May 4, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28465351/an-hnf4%C3%AE-microrna-194-192-signaling-axis-maintains-hepatic-cell-function
#9
Aoi Morimoto, Mana Kannari, Yuichi Tsuchida, Shota Sasaki, Chinatsu Saito, Tsuyoshi Matsuta, Tsukasa Maeda, Megumi Akiyama, Takahiro Nakamura, Masakiyo Sakaguchi, Nobukazu Nameki, Frank J Gonzalez, Yusuke Inoue
HNF4α controls the expression of liver-specific protein-coding genes. However, some microRNAs (miRNAs) are also modulated by HNF4α, and it is not known whether they are direct targets of HNF4α, and whether they influence the hepatic function. In this study, we found that HNF4α regulates miRNAs, indicated by marked down-regulation of miR-194 and miR-192 (miR-194/192) in liver-specific Hnf4a-null (Hnf4a(ΔH)) mice. Transactivation of the shared miR-194/192 promoter was dependent on HNF4α expression, indicating that miR194/192 is a target gene of HNF4α...
May 2, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28446763/hanging-drop-a-best-three-dimensional-3d-culture-method-for-primary-buffalo-and-sheep-hepatocytes
#10
Meena Shri, Himanshu Agrawal, Payal Rani, Dheer Singh, Suneel Kumar Onteru
Livestock, having close resemblance to humans, could be a better source of primary hepatocytes than rodents. Herein, we successfully developed three-dimensional (3D) culturing system for primary sheep and buffalo hepatocytes. The 3D-structures of sheep hepatocytes were formed on the fifth-day and maintained until the tenth-day on polyHEMA-coated plates and in hanging drops with William's E media (HDW). Between the cultured and fresh cells, we observed a similar expression of GAPDH, HNF4α, ALB, CYP1A1, CK8 and CK18...
April 26, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28442500/high-fat-diet-feeding-alters-expression-of-hepatic-drug-metabolizing-enzymes-in-mice
#11
Miaoran Ning, Hyunyoung Jeong
Medical conditions accompanying obesity often require drug therapy, but whether and how obesity alters the expression of drug-metabolizing enzymes and thus drug pharmacokinetics is poorly defined. Previous studies have shown that high fat diet (HFD) feeding and subsequent obesity in mice lead to altered expression of transcriptional regulators for cytochrome P450 (CYP) 2D6, including hepatocyte nuclear factor 4α (HNF4α, a transcriptional activator of CYP2D6) and small heterodimer partner (SHP, a transcriptional repressor of CYP2D6)...
April 25, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/28390038/integrative-transcriptome-analysis-of-liver-cancer-profiles-identifies-upstream-regulators-and-clinical-significance-of-acsm3-gene-expression
#12
Ramani Gopal, Karthikeyan Selvarasu, Ponmathi Panneer Pandian, Kumaresan Ganesan
PURPOSE: Hepatocellular carcinoma (HCC) is one of the most common human malignancies. It has frequently been associated with metabolic perturbations and liver damages. Various members of the family of acyl-CoA synthetases are known to be involved in the production of bioactive fatty acids, and altered expression of its encoding genes has been found to be involved in metabolic perturbations. For the development of novel diagnostic and therapeutic HCC options, a fundamental understanding of the mechanisms associated with the deregulation of candidate genes involved in metabolic perturbation is required...
April 7, 2017: Cellular Oncology (Dordrecht)
https://www.readbyqxmd.com/read/28364040/hypoxia-reduces-hnf4%C3%AE-mody1-protein-expression-in-pancreatic-%C3%AE-cells-by-activating-amp-activated-protein-kinase
#13
Yoshifumi Sato, Tomonori Tsuyama, Chinami Sato, Md Fazlul Karim, Tatsuya Yoshizawa, Masahiro Inoue, Kazuya Yamagata
Hypoxia plays a role in the deterioration of β-cell function. Hepatocyte nuclear factor 4α (HNF4α) has an important role in pancreatic β-cells, and mutations of the human HNF4A gene cause a type of maturity-onset diabetes of the young (MODY1). However, it remains unclear whether hypoxia affects the expression of HNF4α in β-cells. Here, we report that hypoxia reduces HNF4α protein expression in β-cells. Hypoxia-inducible factor (HIF) was not involved in the down-regulation of HNF4α under hypoxic conditions...
March 31, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28352551/an-easy-method-for-preparation-of-cre-loxp-regulated-fluorescent-adenoviral-expression-vectors-and-its-application-for-direct-reprogramming-into-hepatocytes
#14
Chitose Kurihara, Koji Nakade, Jianzhi Pan, Jing Huang, Bohdan Wasylyk, Yuichi Obata
The recombinant adenoviral gene expression system is a powerful tool for gene delivery. However, it is difficult to obtain high titers of infectious virus, principally due to the toxicity of the expressed gene which affects on virus replication in the host HEK293 cells. To avoid these problems, we generated a Cre-loxP-regulated fluorescent universal vector (termed pAxCALRL). This vector produces recombinant adenoviruses that express the red fluorescent protein (RFP) instead of the inserted gene during proliferation, which limits toxicity and can be used to monitor viral replication...
December 2016: Biotechnology Reports
https://www.readbyqxmd.com/read/28334792/gwas-identifies-population-specific-new-regulatory-variants-in-fut6-associated-with-plasma-b12-concentrations-in-indians
#15
Suraj S Nongmaithem, Charudatta V Joglekar, Ghattu V Krishnaveni, Sirazul A Sahariah, Meraj Ahmad, Swetha Ramachandran, Meera Gandhi, Harsha Chopra, Anand Pandit, Ramesh D Potdar, Caroline Hd Fall, Chittaranjan S Yajnik, Giriraj R Chandak
Vitamin B12 is an important cofactor in one-carbon metabolism whose dysregulation is associated with various clinical conditions. Indians have a high prevalence of B12 deficiency but little is known about the genetic determinants of circulating B12 concentrations in Indians. We performed a genome-wide association study in 1001 healthy participants in the Pune Maternal Nutrition Study (PMNS), replication studies in 3418 individuals from other Indian cohorts and by meta-analysis identified new variants, rs3760775 (p = 1...
February 27, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28331449/cyclin-d1-in-the-liver-role-of-noncanonical-signaling-in-liver-steatosis-and-hormone-regulation
#16
Kelley G Núñez, Janet Gonzalez-Rosario, Paul T Thevenot, Ari J Cohen
BACKGROUND: Cyclin D1 is an important protein for cell cycle progression; however, functions independent of the cell cycle have been described in the liver. Cyclin D1 is also involved in DNA repair, is overexpressed in many cancers, and functions as a proto-oncogene. The lesser-known roles of Cyclin D1, specifically in hepatocytes, impact liver steatosis and hormone regulation in the liver. METHODS: A comprehensive search of PubMed was conducted using the keywords Cyclin D1, steatosis, lipogenesis, and liver transplantation...
2017: Ochsner Journal
https://www.readbyqxmd.com/read/28322895/baicalin-benefits-the-anti-hbv-therapy-via-inhibiting-hbv-viral-rnas
#17
COMPARATIVE STUDY
Hai Huang, Wei Zhou, Haiyan Zhu, Pei Zhou, Xunlong Shi
BACKGROUND: Although current antiviral treatments (nucleoside analogs, NAs) for chronic hepatitis B virus (HBV) infection are effective in suppressing HBV-DNA replication, their clinical outcomes can be compromised by the increasing drug resistance and the inefficiency in promoting HBsAg/HBeAg seroconversion. OBJECTIVES: In this study, we will explore possible effects and mechanism of a natural product baicalin (BA) with the anti-HBV efficacy of entecavir (ETV), a first-line anti-HBV drug, in HBV-DNA, HBsAg/HBeAg seroconversion and drug-resistance...
May 15, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28302129/cholesterol-lowing-effect-of-taurine-in-hepg2-cell
#18
Junxia Guo, Ya Gao, Xuelian Cao, Jing Zhang, Wen Chen
BACKGROUND: A number of studies indicate that taurine promotes cholesterol conversion to bile acids by upregulating CYP7A1 gene expression. Few in vitro studies are concerned the concentration change of cholesterol and its product of bile acids, and the molecular mechanism of CYP7A1 induction by taurine. METHODS: The levels of intracellular total cholesterol (TC), free cholesterol (FC), cholesterol ester (EC), total bile acids (TBA) and medium TBA were determined after HepG2 cells were cultured for 24/48 h in DMEM supplemented with taurine at the final concentrations of 1/10/20 mM respectively...
March 16, 2017: Lipids in Health and Disease
https://www.readbyqxmd.com/read/28230250/metformin-attenuates-angiotensin-ii-induced-tgf%C3%AE-1-expression-by-targeting-hepatocyte-nuclear-factor-4%C3%AE
#19
Ruifei Chen, Yenan Feng, Jimin Wu, Yao Song, Hao Li, Qiang Shen, Dan Li, Jianshu Zhang, Zhizhen Lu, Han Xiao, Youyi Zhang
BACKGROUND AND PURPOSE: Metformin, a small molecule antihyperglycaemic agent, is well-known as an AMP-activated protein kinase (AMPK) activator and protects against cardiac fibrosis. However, the underlying mechanisms remain elusive. Transforming growth factor-β1 (TGFβ1) is a key cytokine mediating cardiac fibrosis. Here, we investigated the effects of metformin on TGFβ1 production induced by angiotensin II (AngII) and the underlying mechanisms. EXPERIMENTAL APPROACH: Wild-type and AMPKα2(-/-) C57BL/6 mice were subcutaneously injected with metformin or saline and infused with AngII (3 mg kg(-1) day(-1) ) for 7 days...
February 23, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28217257/regulation-of-hepatic-microrna-expression-by-hepatocyte-nuclear-factor-4-alpha
#20
Hong Lu, Xiaohong Lei, Jerry Liu, Curtis Klaassen
AIM: To uncover the role of hepatocyte nuclear factor 4 alpha (HNF4α) in regulating hepatic expression of microRNAs. METHODS: Microarray and real-time PCR were used to determine hepatic expression of microRNAs in young-adult mice lacking Hnf4α expression in liver (Hnf4α-LivKO). Integrative genomics viewer software was used to analyze the public chromatin immunoprecipitation-sequencing datasets for DNA-binding of HNF4α, RNA polymerase-II, and histone modifications to loci of microRNAs in mouse liver and human hepatoma cells...
February 8, 2017: World Journal of Hepatology
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