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Hepatocyte polarity

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https://www.readbyqxmd.com/read/28105255/pi3k-ship2-pten-pathway-in-cell-polarity-and-hepatitis-c-virus-pathogenesis
#1
REVIEW
Aline Awad, Ama Gassama-Diagne
Hepatitis C virus (HCV) infects hepatocytes, polarized cells in the liver. Chronic HCV infection often leads to steatosis, fibrosis, cirrhosis and hepatocellular carcinoma, and it has been identified as the leading cause of liver transplantation worldwide. The HCV replication cycle is dependent on lipid metabolism and particularly an accumulation of lipid droplets in host cells. Phosphoinositides (PIs) are minor phospholipids enriched in different membranes and their levels are tightly regulated by specific PI kinases and phosphatases...
January 8, 2017: World Journal of Hepatology
https://www.readbyqxmd.com/read/28066964/mechanisms-of-the-prevention-and-inhibition-of-the-progression-and-development-of-nash-by-genetic-and-pharmacological-dcr3-supplementation
#2
Pei-Chang Lee, Ling-Yu Yang, Ying-Wen Wang, Shiang-Fen Huang, Kuei-Chuan Lee, Yun-Cheng Hsieh, Ying-Ying Yang, Shie-Liang Hsieh, Ming-Chih Hou, Han-Chieh Lin, Fa-Yuah Lee, Shou-Dong Lee
AIMS: Treatment to non-alcoholic steatohepatitis (NASH) is difficult due to the absence of a proven treatment and its comprehensive mechanisms. In the NASH animal model, up-regulated hepatic inflammation and oxidative stress with the resultant M1 polarization of macrophage as well as the imbalanced adipocytokines all accelerate NASH progression. As a member of TNF receptor superfamily, decoy receptor 3 (DcR3) not only neutralizes the death ligands, but also performs immune modulations...
January 8, 2017: Hepatology Research: the Official Journal of the Japan Society of Hepatology
https://www.readbyqxmd.com/read/28036299/v-atpase-inhibition-increases-cancer-cell-stiffness-and-blocks-membrane-related-ras-signaling-a-new-option-for-hcc-therapy
#3
Karin Bartel, Maria Winzi, Melanie Ulrich, Andreas Koeberle, Dirk Menche, Oliver Werz, Rolf Müller, Jochen Guck, Angelika M Vollmar, Karin von Schwarzenberg
Hepatocellular carcinoma (HCC) is the fifth most frequent cancer worldwide and the third leading cause of cancer-related death. However, therapy options are limited leaving an urgent need to develop new strategies. Currently, targeting cancer cell lipid and cholesterol metabolism is gaining interest especially regarding HCC. High cholesterol levels support proliferation, membrane-related mitogenic signaling and increase cell softness, leading to tumor progression, malignancy and invasive potential. However, effective ways to target cholesterol metabolism for cancer therapy are still missing...
December 28, 2016: Oncotarget
https://www.readbyqxmd.com/read/28011152/adenosine-a2a-receptor-stimulation-blocks-development-of-nonalcoholic-steatohepatitis-in-mice-by-multilevel-inhibition-of-signals-that-cause-immunolipotoxicity
#4
Elisa Alchera, Simona Rolla, Chiara Imarisio, Valentina Bardina, Guido Valente, Francesco Novelli, Rita Carini
Lipotoxicity and immunoinflammation are associated with the evolution of steatosis toward nonalcoholic steatohepatitis (NASH). This study reports the ability of adenosine A2a receptor (A2aR) activation to inhibit NASH development by modulating the responses of CD4(+) T-helper (Th) cells to avoid an immuno-mediated potentiation of lipotoxicity. The effect of the A2aR agonist CGS21680 on immunoinflammatory signals, CD4(+)Th cell infiltration and immunolipotoxicity was analyzed in steatotic C57BL/6 mice fed with a methionine-choline-deficient (MCD) diet and in mouse hepatocytes exposed to palmitic acid (PA)...
December 6, 2016: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/27923925/biliary-secretion-of-quasi-enveloped-human-hepatitis-a-virus
#5
Asuka Hirai-Yuki, Lucinda Hensley, Jason K Whitmire, Stanley M Lemon
: Hepatitis A virus (HAV) is an unusual picornavirus that is released from cells cloaked in host-derived membranes. These quasi-enveloped virions (eHAV) are the only particle type circulating in blood during infection, whereas only nonenveloped virions are shed in feces. The reason for this is uncertain. Hepatocytes, the only cell type known to support HAV replication in vivo, are highly polarized epithelial cells with basolateral membranes facing onto hepatic (blood) sinusoids and apical membranes abutting biliary canaliculi from which bile is secreted to the gut...
December 6, 2016: MBio
https://www.readbyqxmd.com/read/27916608/functional-properties-of-hepatocytes-in-vitro-are-correlated-with-cell-polarity-maintenance
#6
Anja Zeigerer, Anne Wuttke, Giovanni Marsico, Sarah Seifert, Yannis Kalaidzidis, Marino Zerial
Exploring the cell biology of hepatocytes in vitro could be a powerful strategy to dissect the molecular mechanisms underlying the structure and function of the liver in vivo. However, this approach relies on appropriate in vitro cell culture systems that can recapitulate the cell biological and metabolic features of the hepatocytes in the liver whilst being accessible to experimental manipulations. Here, we adapted protocols for high-resolution fluorescence microscopy and quantitative image analysis to compare two primary hepatocyte culture systems, monolayer and collagen sandwich, with respect to the distribution of two distinct populations of early endosomes (APPL1 and EEA1-positive), endocytic capacity, metabolic and signaling activities...
January 1, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/27909560/induction-of-heme-oxygenase-1-with-dietary-quercetin-reduces-obesity-induced-hepatic-inflammation-through-macrophage-phenotype-switching
#7
Chu-Sook Kim, Hye-Seon Choi, Yeonsoo Joe, Hun Taeg Chung, Rina Yu
BACKGROUND/OBJECTIVES: Obesity-induced steatohepatitis accompanied by activated hepatic macrophages/Kupffer cells facilitates the progression of hepatic fibrinogenesis and exacerbates metabolic derangements such as insulin resistance. Heme oxyganase-1 (HO-1) modulates tissue macrophage phenotypes and thus is implicated in protection against inflammatory diseases. Here, we show that the flavonoid quercetin reduces obesity-induced hepatic inflammation by inducing HO-1, which promotes hepatic macrophage polarization in favor of the M2 phenotype...
December 2016: Nutrition Research and Practice
https://www.readbyqxmd.com/read/27903585/autophagy-in-chronic-liver-diseases-the-two-faces-of-janus
#8
Philippe Gual, Helene Gilgenkrantz, Sophie Lotersztajn
Alcoholic liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD) are the leading causes of cirrhosis and increase the risk of hepatocellular carcinoma and liver-related death. ALD and NAFLD share common pathogenic features extending from isolated steatosis to steatohepatitis, steatofibrosis, which can progress to cirrhosis and hepatocellular carcinoma. The pathophysiological mechanisms of the progression of NAFLD and ALD are complex and still unclear. Important links between the regulation of autophagy (Macroautophagy and Chaperome-mediated autophagy) and chronic liver diseases have been reported...
November 30, 2016: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/27853646/hepatocellular-carcinoma-is-accelerated-by-nash-involving-m2-macrophage-polarization-mediated-by-hif-1%C3%AE-induced-il-10
#9
Aditya Ambade, Abhishek Satishchandran, Banishree Saha, Benedek Gyongyosi, Patrick Lowe, Karen Kodys, Donna Catalano, Gyongyi Szabo
Obesity-related inflammation promotes cancer development. Tissue resident macrophages affect tumor progression and the tumor micro-environment favors polarization into alternatively activated macrophages (M2) that facilitate tumor invasiveness. Here, we dissected the role of western diet-induced NASH in inducing macrophage polarization in a carcinogen initiated model of hepatocellular carcinoma (HCC). Adult C57BL/6 male mice received diethyl nitrosamine (DEN) followed by 24 weeks of high fat-high cholesterol-high sugar diet (HF-HC-HSD)...
2016: Oncoimmunology
https://www.readbyqxmd.com/read/27818736/combined-toxic-effects-of-polar-and-nonpolar-chemicals-on-human-hepatocytes-hepg2-cells-by-quantitative-property-activity-relationship-modeling
#10
Ki-Woong Kim, Yong Lim Won, Dong Jin Park, Young Sun Kim, Eun Sil Jin, Sung Kwang Lee
We determined the toxicity of mixtures of ethyl acetate (EA), isopropyl alcohol (IPA), methyl ethyl ketone (MEK), toluene (TOL) and xylene (XYL) with half-maximal effective concentration (EC50) values obtained using human hepatocytes cells. According to these data, quantitative property-activity relationships (QPAR) models were successfully proposed to predict the toxicity of mixtures by multiple linear regressions (MLR). The leave-one-out cross validation method was used to find the best subsets of descriptors in the learning methods...
October 2016: Toxicological Research
https://www.readbyqxmd.com/read/27792760/ampk-activation-prevents-and-reverses-drug-induced-mitochondrial-and-hepatocyte-injury-by-promoting-mitochondrial-fusion-and-function
#11
Sun Woo Sophie Kang, Ghada Haydar, Caitlin Taniane, Geoffrey Farrell, Irwin M Arias, Jennifer Lippincott-Schwartz, Dong Fu
Mitochondrial damage is the major factor underlying drug-induced liver disease but whether conditions that thwart mitochondrial injury can prevent or reverse drug-induced liver damage is unclear. A key molecule regulating mitochondria quality control is AMP activated kinase (AMPK). When activated, AMPK causes mitochondria to elongate/fuse and proliferate, with mitochondria now producing more ATP and less reactive oxygen species. Autophagy is also triggered, a process capable of removing damaged/defective mitochondria...
2016: PloS One
https://www.readbyqxmd.com/read/27722715/a-vertical-flow-bioreactor-array-compacts-hepatocytes-for-enhanced-polarity-and-functions
#12
Liang Zhu, Huanming Xia, Zhenfeng Wang, Eliza Li Shan Fong, Junjun Fan, Wen Hao Tong, Yen Peng Daphne Seah, Weian Zhang, Qiushi Li, Hanry Yu
Although hepatocytes in vivo experience intra-abdominal pressure (IAP), pressure is typically not incorporated in hepatocyte culture systems. The cuboidal cell shape and extent of intercellular contact between cultured hepatocytes are critical parameters that influence the differentiated hepatic phenotype. Using a microfluidic device, the application of pressure to artificially compact cells and forge cell-cell interactions was previously demonstrated to be effective in accelerating hepatic repolarization. In seeking to implement this approach to higher throughput culture platforms for potential drug screening applications, we specifically designed a vertical-flow compaction bioreactor array (VCBA) that compacts hepatocytes within the range of IAP and portal pressure in vivo in a multi-well setup...
October 5, 2016: Lab on a Chip
https://www.readbyqxmd.com/read/27643636/fabrication-of-3d-culture-platform-with-sandwich-architecture-for-preserving-liver-specific-functions-of-hepatocytes-using-3d-bioprinter
#13
Kenichi Arai, Toshiko Yoshida, Motonori Okabe, Mitsuaki Goto, Tanveer Ahmad Mir, Chika Soko, Yoshinari Tsukamoto, Toshihiro Akaike, Toshio Nikaido, Kaixuan Zhou, Makoto Nakamura
The development of new three-dimensional (3D) cell culture system that maintains the physiologically relevant signals of hepatocytes is essential in drug discovery and tissue engineering research. Conventional two-dimensional (2D) culture yields cell growth, proliferation and differentiation. However, gene expression and signaling profiles can be different from in vivo environment. Here, we report the fabrication of a 3D culture system using an artificial scaffold and our custom-made inkjet 3D-bioprinter as a new strategy for studying liver-specific functions of hepatocytes...
September 19, 2016: Journal of Biomedical Materials Research. Part A
https://www.readbyqxmd.com/read/27642075/liver-serine-palmitoyltransferase-activity-deficiency-in-early-life-impairs-adherens-junctions-and-promotes-tumorigenesis
#14
Zhiqiang Li, Inamul Kabir, Hui Jiang, Hongwen Zhou, Jenny Libien, Jianying Zeng, Albert Stanek, Peiqi Ou, Kailyn R Li, Shane Zhang, Hai H Bui, Ming-Shang Kuo, Tae-Sik Park, Benjamin Kim, Tilla S Worgall, Chongmin Huan, Xian-Cheng Jiang
: Serine palmitoyltransferase is the key enzyme in sphingolipid biosynthesis. Mice lacking serine palmitoyltransferase are embryonic lethal. We prepared liver-specific mice deficient in the serine palmitoyltransferase long chain base subunit 2 gene using an albumin-cyclization recombination approach and found that the deficient mice have severe jaundice. Moreover, the deficiency impairs hepatocyte polarity, attenuates liver regeneration after hepatectomy, and promotes tumorigenesis. Importantly, we show that the deficiency significantly reduces sphingomyelin but not other sphingolipids in hepatocyte plasma membrane; greatly reduces cadherin, the major protein in adherens junctions, on the membrane; and greatly induces cadherin phosphorylation, an indication of its degradation...
December 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/27626926/differential-lipotoxic-effects-of-palmitate-and-oleate-in-activated-human-hepatic-stellate-cells-and-epithelial-hepatoma-cells
#15
Alexandra M Hetherington, Cynthia G Sawyez, Emma Zilberman, Alexandra M Stoianov, Debra L Robson, Nica M Borradaile
BACKGROUND/AIMS: Nonalcoholic fatty liver disease (NAFLD) progression to fibrosis, cirrhosis and hepatocellular carcinoma, alters the cellular composition of this organ. During late-stage NAFLD, fibrotic and possibly cancerous cells can proliferate and, like normal hepatocytes, are exposed to high concentrations of fatty acids from both surrounding tissue and circulating lipid sources. We hypothesized that primary human activated hepatic stellate cells and epithelial hepatoma (HepG2) cells respond differently to lipotoxic conditions, and investigated the mechanisms involved...
2016: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/27600198/expression-of-claudins-occludin-junction-adhesion-molecule-a-and-zona-occludens-1-in-canine-organs
#16
Changhwan Ahn, Da-Hye Shin, Dongoh Lee, Su-Myung Kang, Ju-Hyung Seok, Hee Young Kang, Eui-Bae Jeung
Tight junctions are the outermost structures of intercellular junctions and are classified as transmembrane proteins. These factors form selective permeability barriers between cells, act as paracellular transporters and regulate structural and functional polarity of cells. Although tight junctions have been previously studied, comparison of the transcriptional‑translational levels of these molecules in canine organs remains to be investigated. In the present study, organ‑specific expression of the tight junction proteins, claudin, occludin, junction adhesion molecule A and zona occludens 1 was examined in the canine duodenum, lung, liver and kidney...
October 2016: Molecular Medicine Reports
https://www.readbyqxmd.com/read/27501956/the-leishmanicidal-activity-of-oleuropein-is-selectively-regulated-through-inflammation-and-oxidative-stress-related-genes
#17
Ioannis D Kyriazis, Olga S Koutsoni, Nektarios Aligiannis, Kalliopi Karampetsou, Alexios-Leandros Skaltsounis, Eleni Dotsika
BACKGROUND: Much research effort has been focused on investigating new compounds derived from low-cost sources, such as natural products, for treating leishmaniasis. Oleuropein derived from numerous plants, particularly from the olive tree, Olea europaea L. (Oleaceae), is a biophenol with many biological activities. Our previous findings showed that oleuropein exhibits leishmanicidal effects against three Leishmania spp. in vitro, and minimizes the parasite burden in L. donovani-infected BALB/c mice...
2016: Parasites & Vectors
https://www.readbyqxmd.com/read/27470567/antidiabetic-antihyperlipidemic-and-anti-inflammatory-effects-of-tilianin-in-streptozotocin-nicotinamide-diabetic-rats
#18
Jorge Alberto García-Díaz, Gabriel Navarrete-Vázquez, Sara García-Jiménez, Sergio Hidalgo-Figueroa, Julio C Almanza-Pérez, Francisco Javier Alarcón-Aguilar, Jaime Gómez-Zamudio, Miguel Cruz, Maximiliano Ibarra-Barajas, Samuel Estrada-Soto
Flavonoids from medicinal plants have been used in traditional medicine to treat a variety of prevalent diseases. Flavones activate the signaling pathways promoting fuel metabolism and insulin sensitizing in hepatocytes and adipocytes, which suggests that flavones may have the potential to exert in vivo antidiabetic and antihyperlipidemic effects. Thus, the aim of the current study was to determine the antidiabetic, antihyperlipidemic and anti-inflammatory effects of tilianin in diabetic rats. Also, to understand the mechanism involved using in vitro 3T3-L1 cells and tissues from experimental animals treated with test samples through molecular profile studies...
October 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27453055/m1-m2-macrophage-polarization-in-pseudolobules-consisting-of-adipohilin-rich-hepatocytes-in-thioacetamide-taa-induced-rat-hepatic-cirrhosis
#19
Kavindra Kumara Wijesundera, Takeshi Izawa, Anusha Hemamali Tennakoon, Hossain Md Golbar, Miyuu Tanaka, Mitsuru Kuwamura, Jyoji Yamate
INTRODUCTION: Liver steatosis is the most frequent liver disease and may further develop into non-alcoholic steatohepatitis (NASH), liver cirrhosis, and finally hepatocellular carcinoma. Adipophilin (Adp) is localized on lipid droplet membrane in cytoplasm, and its increased expression is related to development of steatosis and NASH. The relationship between M1-/M2-macrophage polarization and Adp-rich hepatocyte-consisting pseudolobules (PLs) was investigated in thioacetamide (TAA)-induced rat cirrhosis...
August 2016: Experimental and Molecular Pathology
https://www.readbyqxmd.com/read/27421950/functional-maturation-of-induced-pluripotent-stem-cell-hepatocytes-in-extracellular-matrix-a-comparative-analysis-of-bioartificial-liver-microenvironments
#20
Bo Wang, Adam E Jakus, Pedro M Baptista, Shay Soker, Alejandro Soto-Gutierrez, Michael M Abecassis, Ramille N Shah, Jason A Wertheim
UNLABELLED: : Induced pluripotent stem cells (iPSCs) are new diagnostic and potentially therapeutic tools to model disease and assess the toxicity of pharmaceutical medications. A common limitation of cell lineages derived from iPSCs is a blunted phenotype compared with fully developed, endogenous cells. We examined the influence of novel three-dimensional bioartificial microenvironments on function and maturation of hepatocyte-like cells differentiated from iPSCs and grown within an acellular, liver-derived extracellular matrix (ECM) scaffold...
September 2016: Stem Cells Translational Medicine
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