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https://www.readbyqxmd.com/read/28812950/expression-of-cytochrome-p450-regulators-in-cynomolgus-macaque
#1
Yasuhiro Uno, Hiroshi Yamazaki
1. Cytochrome P450 (P450) regulators including nuclear receptors and transcription factors have not been fully investigated in cynomolgus macaques, an important species used in drug metabolism studies. In this study, we analyzed seventeen P450 regulators by sequence and phylogenetic analysis, and tissue expression. 2. Gene and genome structures of seventeen P450 regulators were similar to the human orthologs, and the deduced amino acid sequences showed high sequence identities (92-95%) and more closely clustered, with the human orthologs...
August 16, 2017: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/28807057/inhibitory-effects-of-hnf4%C3%AE-on-migration-maltransformation-of-hepatic-progenitors-hnf4%C3%AE-overexpressing-hepatic-progenitors-for-liver-repopulation
#2
Ping Wang, Min Cong, Tianhui Liu, Hufeng Xu, Lin Wang, Guangyong Sun, Aiting Yang, Dong Zhang, Jian Huang, Yameng Sun, Wenshan Zhao, Hong Ma, Jidong Jia, Hong You
BACKGROUND: Although they are expandable in vitro, hepatic progenitors are immature cells and share many immunomarkers with hepatocellular carcinoma, raising potential concerns regarding maltransformation after transplantation. This study investigated the effects of hepatic nuclear factor (HNF) 4α on the proliferation, migration, and maltransformation of hepatic progenitors and determined the feasibility of using these manipulated cells for transplantation. METHODS: The effects of HNF4α on rat hepatic progenitors (i...
August 14, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28745269/hepatitis-b-virus-prevents-excessive-viral-production-via-reduction-of-cell-death-inducing-dff45-like-effectors
#3
Jun Yasumoto, Hirotake Kasai, Kentaro Yoshimura, Teruhime Otoguro, Koichi Watashi, Takaji Wakita, Atsuya Yamashita, Tomohisa Tanaka, Sen Takeda, Kohji Moriishi
The relationship between hepatitis B virus (HBV) infection and lipid accumulation remains largely unknown. In this study, we investigated the effect of HBV propagation on lipid droplet growth in HBV-infected cells and HBV-producing cell lines, HepG2.2.15 and HBV-inducible Hep38.7-Tet. The amount of intracellular triglycerides was significantly reduced in HBV-infected and HBV-producing cells compared with HBV-lacking control cells. Electron and immunofluorescent microscopic analyses showed that the average size of a single lipid droplet (LD) was significantly less in the HBV-infected and HBV-producing cells than in the HBV-lacking control cells...
July 2017: Journal of General Virology
https://www.readbyqxmd.com/read/28740077/footprint-free-human-fetal-foreskin-derived-ipscs-a-tool-for-modeling-hepatogenesis-associated-gene-regulatory-networks
#4
Peggy Matz, Wasco Wruck, Beatrix Fauler, Diran Herebian, Thorsten Mielke, James Adjaye
Induced pluripotent stem cells (iPSCs) are similar to embryonic stem cells and can be generated from somatic cells. We have generated episomal plasmid-based and integration-free iPSCs (E-iPSCs) from human fetal foreskin fibroblast cells (HFF1). We used an E-iPSC-line to model hepatogenesis in vitro. The HLCs were characterized biochemically, i.e. glycogen storage, ICG uptake and release, UREA and bile acid production, as well as CYP3A4 activity. Ultra-structure analysis by electron microscopy revealed the presence of lipid and glycogen storage, tight junctions and bile canaliculi- all typical features of hepatocytes...
July 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28724938/a-novel-role-for-rar%C3%AE-agonists-as-apolipoprotein-ciii-inhibitors-identified-from-high-throughput-screening
#5
Sang Jun Lee, Madhupriya Mahankali, Abdallah Bitar, Huafei Zou, Elizabeth Chao, Hung Nguyen, Jose Gonzalez, Dawna Caballero, Mitch Hull, Danling Wang, Peter G Schultz, Weijun Shen
Elevated triglyceride (TG) levels are well-correlated with the risk for cardiovascular disease (CVD). Apolipoprotein CIII (ApoC-III) is a key regulator of plasma TG levels through regulation of lipolysis and lipid synthesis. To identify novel regulators of TG levels, we carried out a high throughput screen (HTS) using an ApoC-III homogenous time resolved fluorescence (HTRF) assay. We identified several retinoic acid receptor (RAR) agonists that reduced secreted ApoC-III levels in human hepatic cell lines. The RARα specific agonist AM580 inhibited secreted ApoC-III by >80% in Hep3B cells with an EC50 ~2...
July 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28655781/hepatocyte-specific-hnf4%C3%AE-mir-122-pathway-contributes-to-the-iron-overload-mediated-hepatic-inflammation
#6
Min Li, Yuxiao Tang, Lusha Wu, Fengfeng Mo, Xin Wang, Hongxia Li, Ruirui Qi, Hongwei Zhang, Arun Srivastava, Chen Ling
Hepatic iron-overload (IO) is one of the major complications of transfusional therapy. It was generally thought that IO triggers substantial inflammatory responses by producing reactive oxygen species in hepatic macrophages. Recently, decrease of microRNA-122 was observed in a genetic knockout (Hfe-/-) mouse model of IO. Since hepatocyte-enriched miR-122 is known as a key regulator of multiple hepatic pathways including inflammation, it is of interest whether hepatocyte directly contributes to the IO-mediated hepatic inflammation...
June 27, 2017: Blood
https://www.readbyqxmd.com/read/28641979/sexual-dimorphism-in-the-fetal-cardiac-response-to-maternal-nutrient-restriction
#7
Sribalasubashini Muralimanoharan, Cun Li, Ernesto S Nakayasu, Cameron P Casey, Thomas O Metz, Peter W Nathanielsz, Alina Maloyan
Poor maternal nutrition causes intrauterine growth restriction (IUGR); however, its effects on fetal cardiac development are unclear. We have developed a baboon model of moderate maternal undernutrition, leading to IUGR. We hypothesized that the IUGR affects fetal cardiac structure and metabolism. Six control pregnant baboons ate ad-libitum (CTRL)) or 70% CTRL from 0.16 of gestation (G). Fetuses were euthanized at C-section at 0.9G under general anesthesia. Male but not female IUGR fetuses showed left ventricular fibrosis inversely correlated with birth weight...
July 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28627437/molecular-characterization-and-functional-analysis-of-ppar%C3%AE-promoter-in-yellow-catfish-pelteobagrus-fulvidraco
#8
Wen-Jing You, Yao-Fang Fan, Yi-Huan Xu, Kun Wu, Xiao-Ying Tan
Peroxisome proliferator-activated receptor α (PPARα) is a ligand-activated transcription factor that plays critical roles in the regulation of many important physiological processes. In the present study, the 1686-bp PPARα promoter for yellow catfish Pelteobagrus fulvidraco was first cloned and characterized. The transcription start site (TSS) of PPARα gene was mapped using RLM-5'RACE method. The luciferase vectors were constructed and transiently transfected into HepG2 cells and HEK293 cells, respectively, for functional analysis of promoters...
September 5, 2017: Gene
https://www.readbyqxmd.com/read/28577958/lepidic-predominant-adenocarcinoma-and-invasive-mucinous-adenocarcinoma-of-the-lung-exhibit-specific-mucin-expression-in-relation-with-oncogenic-drivers
#9
Duruisseaux Michaël, Antoine Martine, Rabbe Nathalie, Rodenas Anita, Mc Leer-Florin Anne, Lacave Roger, Poulot Virginie, Duchêne Belinda, Van Seuningen Isabelle, Cadranel Jacques, Wislez Marie
OBJECTIVES: To evaluate MUC1, MUC2, MUC5B, MUC5AC, and MUC6 expression in invasive lepidic predominant adenocarcinoma (LPA) and invasive mucinous adenocarcinoma (IMA) of the lung, and the impact of oncogenic drivers. MATERIALS AND METHODS: MUC1, MUC2, MUC5B, MUC5AC, MUC6, TTF1 and Hnf4α immunohistochemistry was performed on surgical samples from 52 patients with IMA (n=25) or LPA (n=27). We searched for EGFR, KRAS, BRAF, and HER2 mutations and ALK, ROS1, and NRG1 rearrangements...
July 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/28565878/ginsenoside-rb3-strengthens-the-hypoglycemic-effect-through-ampk-for-inhibition-of-hepatic-gluconeogenesis
#10
Fanli Meng, Xiaotian Su, Wei Li, Yinan Zheng
Ginsenoside Rb3 is one of the major active components in protopanaxdiol type ginsenosides, and has demonstrated anti-diabetic activity. However, the mechanism of this action has yet to be elucidated. The present study investigated the effects of ginsenoside Rb3 on the AMP-activated protein kinase (AMPK) gluconeogenesis pathway. The present study involved the use of HepG2 cells and western blot analysis to systematically evaluate the effect of ginsenoside Rb3 on AMPK signaling proteins and key factors of gluconeogenesis [phosphoenolpyruvate carboxykinase (PEPCK), glucose-6-phosphatase, forkhead transcription factor 1 (FOXO1) and hepatic nuclear receptor 4α (HNF4α)]...
May 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28557353/generation-of-carbamoyl-phosphate-synthetase-1-reporter-cell-lines-for-the-assessment-of-ammonia-metabolism
#11
Yi Wang, Le Chang, Jiahui Zhai, Qiao Wu, Donggen Wang, Yunfang Wang
Both primary hepatocytes and stem cells-derived hepatocyte-like cells (HLCs) are major sources for bioartificial liver (BAL). Maintenance of hepatocellular functions and induction of functional maturity of HLCs are critical for BAL's support effect. It remains difficult to assess and improve detoxification functions inherent to hepatocytes, including ammonia clearance. Here, we aim to assess ammonia metabolism and identify ammonia detoxification enhancer by developing an imaging strategy. In hepatoma cell line HepG2, and immortalized hepatic cell line LO2, carbamoyl phosphate synthetase 1 (CPS1) gene, the first enzyme of ammonia-eliminating urea cycle, was labelled with fluorescence protein via CRISPR/Cas9 system...
May 30, 2017: Journal of Cellular and Molecular Medicine
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
#12
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
#13
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
#14
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...
July 1, 2017: Life Sciences
https://www.readbyqxmd.com/read/28499695/dapagliflozin-modulates-glucagon-secretion-in-an-sglt2-independent-manner-in-murine-alpha-cells
#15
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
#16
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...
July 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
#17
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
#18
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...
August 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
#19
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
#20
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
Hepatocyte nuclear factor 4α (HNF4α) controls the expression of liver-specific protein-coding genes. However, some microRNAs are also modulated by HNF4α, and it is not known whether they are direct targets of HNF4α and whether they influence hepatic function. In this study, we found that HNF4α regulates microRNAs, 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 miR-194/192 is a target gene of HNF4α...
June 23, 2017: Journal of Biological Chemistry
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