Summary: The main structural component of the LIVER. They are specialized EPITHELIAL CELLS that are organized into interconnected plates called lobules.

Top Publications

  1. pmc Role of AMP-activated protein kinase in mechanism of metformin action
    G Zhou
    Department of Molecular Endocrinology, Merck Research Laboratories, Rahway, New Jersey 07065, USA
    J Clin Invest 108:1167-74. 2001
  2. pmc Metformin inhibits hepatic gluconeogenesis in mice independently of the LKB1/AMPK pathway via a decrease in hepatic energy state
    Marc Foretz
    Institut Cochin, Universite Paris Descartes, CNRS UMR 8104, Paris, France
    J Clin Invest 120:2355-69. 2010
  3. ncbi Induction of functional hepatocyte-like cells from mouse fibroblasts by defined factors
    Pengyu Huang
    Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy for Sciences, Yueyang Road 320, 200031 Shanghai, China
    Nature 475:386-9. 2011
  4. pmc Liver regeneration
    George K Michalopoulos
    Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, USA
    J Cell Physiol 213:286-300. 2007
  5. ncbi The CREB coactivator TORC2 is a key regulator of fasting glucose metabolism
    Seung Hoi Koo
    Peptide Biology Laboratories, Salk Institute for Biological Studies, 10010 N Torrey Pines Rd, La Jolla, California 92037 1002, USA
    Nature 437:1109-11. 2005
  6. ncbi NF-kappaB functions as a tumour promoter in inflammation-associated cancer
    Eli Pikarsky
    Department of Pathology, Hadassah Hebrew University Medical Center, Jerusalem 91120, Israel
    Nature 431:461-6. 2004
  7. ncbi Direct conversion of mouse fibroblasts to hepatocyte-like cells by defined factors
    Sayaka Sekiya
    Division of Organogenesis and Regeneration, Medical Institute of Bioregulation, Kyushu University, 3 1 1 Maidashi, Higashi ku, Fukuoka 812 8582, Japan
    Nature 475:390-3. 2011
  8. pmc Highly efficient generation of human hepatocyte-like cells from induced pluripotent stem cells
    Karim Si-Tayeb
    Department of Cell Biology, Division of Pediatric Pathology, Medical College of Wisconsin, Milwaukee, WI 53226, USA
    Hepatology 51:297-305. 2010
  9. ncbi Senescence surveillance of pre-malignant hepatocytes limits liver cancer development
    Tae Won Kang
    Helmholtz Centre for Infection Research, Inhoffenstrasse 7, 38124 Braunschweig, Germany
    Nature 479:547-51. 2011
  10. ncbi Hepatic fibroblast growth factor 21 is regulated by PPARalpha and is a key mediator of hepatic lipid metabolism in ketotic states
    Michael K Badman
    Division of Endocrinology, Department of Medicine, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA 02215, USA
    Cell Metab 5:426-37. 2007

Detail Information

Publications363 found, 100 shown here

  1. pmc Role of AMP-activated protein kinase in mechanism of metformin action
    G Zhou
    Department of Molecular Endocrinology, Merck Research Laboratories, Rahway, New Jersey 07065, USA
    J Clin Invest 108:1167-74. 2001
    ..Here we report that metformin activates AMPK in hepatocytes; as a result, acetyl-CoA carboxylase (ACC) activity is reduced, fatty acid oxidation is induced, and expression ..
  2. pmc Metformin inhibits hepatic gluconeogenesis in mice independently of the LKB1/AMPK pathway via a decrease in hepatic energy state
    Marc Foretz
    Institut Cochin, Universite Paris Descartes, CNRS UMR 8104, Paris, France
    J Clin Invest 120:2355-69. 2010
    ..b>Hepatocytes lacking AMPK displayed normal glucose production and gluconeogenic gene expression compared with wild-type ..
  3. ncbi Induction of functional hepatocyte-like cells from mouse fibroblasts by defined factors
    Pengyu Huang
    Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy for Sciences, Yueyang Road 320, 200031 Shanghai, China
    Nature 475:386-9. 2011
    The generation of functional hepatocytes independent of donor liver organs is of great therapeutic interest with regard to regenerative medicine and possible cures for liver disease...
  4. pmc Liver regeneration
    George K Michalopoulos
    Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, USA
    J Cell Physiol 213:286-300. 2007
    ..In situations when hepatocytes or biliary cells are blocked from regeneration, these cell types can function as facultative stem cells for ..
  5. ncbi The CREB coactivator TORC2 is a key regulator of fasting glucose metabolism
    Seung Hoi Koo
    Peptide Biology Laboratories, Salk Institute for Biological Studies, 10010 N Torrey Pines Rd, La Jolla, California 92037 1002, USA
    Nature 437:1109-11. 2005
    ..Individuals with type 2 diabetes often exhibit fasting hyperglycaemia due to elevated gluconeogenesis; compounds that enhance TORC2 phosphorylation may offer therapeutic benefits in this setting...
  6. ncbi NF-kappaB functions as a tumour promoter in inflammation-associated cancer
    Eli Pikarsky
    Department of Pathology, Hadassah Hebrew University Medical Center, Jerusalem 91120, Israel
    Nature 431:461-6. 2004
    ..induction of IkappaB-super-repressor in later stages of tumour development resulted in apoptosis of transformed hepatocytes and failure to progress to hepatocellular carcinoma...
  7. ncbi Direct conversion of mouse fibroblasts to hepatocyte-like cells by defined factors
    Sayaka Sekiya
    Division of Organogenesis and Regeneration, Medical Institute of Bioregulation, Kyushu University, 3 1 1 Maidashi, Higashi ku, Fukuoka 812 8582, Japan
    Nature 475:390-3. 2011
    ..Normally, hepatocytes differentiate from hepatic progenitor cells to form the liver during development...
  8. pmc Highly efficient generation of human hepatocyte-like cells from induced pluripotent stem cells
    Karim Si-Tayeb
    Department of Cell Biology, Division of Pediatric Pathology, Medical College of Wisconsin, Milwaukee, WI 53226, USA
    Hepatology 51:297-305. 2010
    ..In addition to their therapeutic potential, primary human hepatocytes facilitate the study of molecular and genetic aspects of human hepatic disease and development and provide a ..
  9. ncbi Senescence surveillance of pre-malignant hepatocytes limits liver cancer development
    Tae Won Kang
    Helmholtz Centre for Infection Research, Inhoffenstrasse 7, 38124 Braunschweig, Germany
    Nature 479:547-51. 2011
    ..Here we show that oncogene-induced senescence occurs in otherwise normal murine hepatocytes in vivo...
  10. ncbi Hepatic fibroblast growth factor 21 is regulated by PPARalpha and is a key mediator of hepatic lipid metabolism in ketotic states
    Michael K Badman
    Division of Endocrinology, Department of Medicine, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA 02215, USA
    Cell Metab 5:426-37. 2007
    ..These findings identify hepatic FGF21 as a critical regulator of lipid homeostasis and identify a physiological role for this hepatic hormone...
  11. ncbi Endocrine regulation of the fasting response by PPARalpha-mediated induction of fibroblast growth factor 21
    Takeshi Inagaki
    Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
    Cell Metab 5:415-25. 2007
    ..These findings demonstrate an unexpected role for the PPARalpha-FGF21 endocrine signaling pathway in regulating diverse metabolic and behavioral aspects of the adaptive response to starvation...
  12. pmc Infectious hepatitis C virus pseudo-particles containing functional E1-E2 envelope protein complexes
    Birke Bartosch
    Laboratoire de Vectorologie Rétrovirale et Thérapie Génique, Institut National de la Santé et de la Recherche Médicale U412, IFR 128, Ecole Normale Superieure de Lyon, 69364 Lyon Cedex 07, France
    J Exp Med 197:633-42. 2003
    ..Primary hepatocytes as well as hepato-carcinoma cells were found to be the major targets of infection in vitro...
  13. ncbi In vitro hepatic differentiation of human mesenchymal stem cells
    Kuan Der Lee
    Division of Cancer Research, National Health Research Institutes, Taiwan
    Hepatology 40:1275-84. 2004
    ..After 4 weeks of induction, cuboidal morphology, which is characteristic of hepatocytes, was observed, and cells also expressed marker genes specific of liver cells in a time-dependent manner...
  14. ncbi The liver as a lymphoid organ
    Ian Nicholas Crispe
    David H Smith Center for Vaccine Biology and Immunology, Aab Institute for Biomedical Research, University of Rochester Medical Center, Rochester, New York 14642, USA
    Annu Rev Immunol 27:147-63. 2009
    ..Important human pathogens, including hepatitis C virus and the malaria parasite, exploit the liver's environment, subvert immunity, and establish persistent infection...
  15. pmc Generation and regeneration of cells of the liver and pancreas
    Kenneth S Zaret
    Epigenetics and Progenitor Cells Program, Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA 19111, USA
    Science 322:1490-4. 2008
    ..Interest in the development and regeneration of the organs has been fueled by the intense need for hepatocytes and pancreatic beta cells in the therapeutic treatment of liver failure and type I diabetes...
  16. pmc Fate tracing of mature hepatocytes in mouse liver homeostasis and regeneration
    Yann Malato
    Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, UCSF, San Francisco, California, USA
    J Clin Invest 121:4850-60. 2011
    ..that homeostasis and regeneration of the adult liver are mediated by self duplication of lineage-restricted hepatocytes and biliary epithelial cells...
  17. pmc Hepatocyte-specific deletion of SIRT1 alters fatty acid metabolism and results in hepatic steatosis and inflammation
    Aparna Purushotham
    Laboratory of Signal Transduction, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA
    Cell Metab 9:327-38. 2009
    ..Taken together, our data indicate that SIRT1 plays a vital role in the regulation of hepatic lipid homeostasis and that pharmacological activation of SIRT1 may be important for the prevention of obesity-associated metabolic diseases...
  18. pmc Infection of a human hepatoma cell line by hepatitis B virus
    Philippe Gripon
    Institut National de la Santé et de la Recherche Médicale INSERM U522, Hopital de Pontchaillou, 35033 Rennes, France
    Proc Natl Acad Sci U S A 99:15655-60. 2002
    ..expresses specific hepatocyte functions, and supports HBV infection as well as primary cultures of normal human hepatocytes. Differentiation and infectability are maintained only when these cells are cultured in the presence of ..
  19. pmc Inductive angiocrine signals from sinusoidal endothelium are required for liver regeneration
    Bi Sen Ding
    Howard Hughes Medical Institute, Ansary Stem Cell Institute, and Department of Genetic Medicine, Weill Cornell Medical College, New York, New York 10065, USA
    Nature 468:310-5. 2010
    ..Therapeutic co-transplantation of inductive VEGFR2(+)Id1(+)Wnt2(+)HGF(+) LSECs with hepatocytes provides an effective strategy to achieve durable liver regeneration.
  20. ncbi Defects in adaptive energy metabolism with CNS-linked hyperactivity in PGC-1alpha null mice
    Jiandie Lin
    Dana Farber Cancer Institute and Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
    Cell 119:121-35. 2004
    ..We show here that, while hepatocytes lacking PGC-1alpha are defective in the program of hormone-stimulated gluconeogenesis, the mice have ..
  21. pmc MicroRNA-217 promotes ethanol-induced fat accumulation in hepatocytes by down-regulating SIRT1
    Huquan Yin
    Department of Molecular Pharmacology, University of South Florida Health Sciences Center, Tampa, Florida 33612, USA
    J Biol Chem 287:9817-26. 2012
    ..The role of miR-217 in the regulation of the effects of ethanol was investigated in cultured mouse AML-12 hepatocytes and in the livers of chronically ethanol-fed mice...
  22. pmc Glucagon-like peptide-1 receptor is present on human hepatocytes and has a direct role in decreasing hepatic steatosis in vitro by modulating elements of the insulin signaling pathway
    Nitika Arora Gupta
    Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322, USA
    Hepatology 51:1584-92. 2010
    ..In this study, we demonstrate that exendin-4/GLP-1 has a cognate receptor on human hepatocytes and that exendin-4 has a direct effect on the reduction of hepatic steatosis in the absence of insulin...
  23. ncbi Nonalcoholic steatohepatitis: association of insulin resistance and mitochondrial abnormalities
    A J Sanyal
    Division of Gastroenterology Hepatology, Department of Internal Medicine, Virginia Commonwealth University Medical College of Virginia, Richmond, Virginia 23298 0711, USA
    Gastroenterology 120:1183-92. 2001
    ..of free fatty acids (FFA) to the liver, and hepatic fatty acid beta oxidation, thereby creating oxidative stress; and (2) an abnormality within the hepatocytes that might render them more susceptible to injury from oxidative stress.
  24. pmc Interleukin-22 but not interleukin-17 provides protection to hepatocytes during acute liver inflammation
    Lauren A Zenewicz
    Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA
    Immunity 27:647-59. 2007
    ..b>Hepatocytes from mice deficient in IL-22 were highly sensitive to the detrimental immune response associated with hepatitis...
  25. ncbi Mitochondrial injury, oxidative stress, and antioxidant gene expression are induced by hepatitis C virus core protein
    Michiari Okuda
    Department of Physiology and Biophysics, University of Texas Medical Branch, Galveston, Texas 77555 0641, USA
    Gastroenterology 122:366-75. 2002
    ..Indirect evidence suggests that oxidative stress and mitochondrial injury play a role. The aim of this study was to determine if the HCV core protein itself alters mitochondrial function and contributes to oxidative stress...
  26. pmc HepatoNet1: a comprehensive metabolic reconstruction of the human hepatocyte for the analysis of liver physiology
    Christoph Gille
    Institute of Biochemistry, University Medicine Charité Berlin, Berlin, Germany
    Mol Syst Biol 6:411. 2010
  27. ncbi Paraoxonase 1 (PON1) expression in hepatocytes is upregulated by pomegranate polyphenols: a role for PPAR-gamma pathway
    Jasmin Khateeb
    The Lipid Research Laboratory, Technion Faculty of Medicine, The Rappaport Family Institute for Research in the Medical Sciences, and Rambam Medical Center, Haifa, Israel
    Atherosclerosis 208:119-25. 2010
    ..Because promoter sequence of PON1 gene indicates that it could be regulated by nuclear receptors, we investigated the effect of PJ polyphenols on PON1 gene expression in HuH7 hepatocytes.
  28. ncbi Generation of functional hepatocytes from human embryonic stem cells under chemically defined conditions that recapitulate liver development
    Thomas Touboul
    Institut National de la Sante et de la Recherche Medicale, INSERM, Unite 972, IFR 93, Bicetre Hospital, Kremlin Bicetre, France corrected
    Hepatology 51:1754-65. 2010
    Generation of hepatocytes from human embryonic stem cells (hESCs) could represent an advantageous source of cells for cell therapy approaches as an alternative to orthotopic liver transplantation...
  29. pmc GRP78 expression inhibits insulin and ER stress-induced SREBP-1c activation and reduces hepatic steatosis in mice
    Hélène L Kammoun
    INSERM, UMR S, Centre de Recherche des Cordeliers, Paris, France
    J Clin Invest 119:1201-15. 2009
    ..Interestingly, GRP78 overexpression also inhibited insulin-induced SREBP-1c cleavage in cultured primary hepatocytes. These findings demonstrate that GRP78 inhibits both insulin-dependent and ER stress-dependent SREBP-1c ..
  30. ncbi Liver: An organ with predominant innate immunity
    Bin Gao
    Section on Liver Biology, Laboratory of Physiologic Studies, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20892, USA
    Hepatology 47:729-36. 2008
    ..In addition, the liver also plays an important role in controlling systemic innate immunity through the biosynthesis of numerous soluble pathogen-recognition receptors and complement components...
  31. pmc Hepatitis C virus production by human hepatocytes dependent on assembly and secretion of very low-density lipoproteins
    Hua Huang
    Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX 75390 9046, USA
    Proc Natl Acad Sci U S A 104:5848-53. 2007
    ..Hepatitis C virus (HCV) and triglyceride-rich very low-density lipoproteins (VLDLs) both are secreted uniquely by hepatocytes and circulate in blood in a complex...
  32. ncbi Insulin- and leptin-mediated control of aquaglyceroporins in human adipocytes and hepatocytes is mediated via the PI3K/Akt/mTOR signaling cascade
    Amaia Rodríguez
    Metabolic Research Laboratory, University of Navarra, 31080 Pamplona, Spain
    J Clin Endocrinol Metab 96:E586-97. 2011
    ..The impact of obesity and obesity-associated type 2 diabetes as well as the potential regulatory role of insulin and leptin on aquaglyceroporins (AQP) 3, 7, and 9 were analyzed...
  33. pmc SIRT1 regulates hepatocyte lipid metabolism through activating AMP-activated protein kinase
    Xiuyun Hou
    Vascular Biology Unit and Molecular Cardiology Unit, Whitaker Cardiovascular Institute, Boston University School of Medicine, and Section of Endocrinology, Boston University, Boston, MA 02118, USA
    J Biol Chem 283:20015-26. 2008
    ..carboxylase), elevation in expression of FAS (fatty acid synthase), and lipid accumulation in human HepG2 hepatocytes exposed to high glucose...
  34. pmc Modeling inherited metabolic disorders of the liver using human induced pluripotent stem cells
    S Tamir Rashid
    Laboratory for Regenerative Medicine, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK
    J Clin Invest 120:3127-36. 2010
    ..Each line was differentiated into hepatocytes using what we believe to be a novel 3-step differentiation protocol in chemically defined conditions...
  35. ncbi Monoclonal anti-claudin 1 antibodies prevent hepatitis C virus infection of primary human hepatocytes
    Isabel Fofana
    INSERM, U748, Strasbourg, France
    Gastroenterology 139:953-64, 964.e1-4. 2010
    ..The tight junction protein claudin-1 (CLDN1) has been shown to be required for entry of HCV into the cell...
  36. ncbi miR-122, a paradigm for the role of microRNAs in the liver
    Muriel Girard
    INSERM, U781, Paris 75015, France
    J Hepatol 48:648-56. 2008
    ..We provide a compilation of all miRNAs expressed in the liver, and consider some possible therapeutic opportunities for exploiting miRNAs in the different settings of liver diseases...
  37. pmc Bifurcation of insulin signaling pathway in rat liver: mTORC1 required for stimulation of lipogenesis, but not inhibition of gluconeogenesis
    Shijie Li
    Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX 75390 9046, USA
    Proc Natl Acad Sci U S A 107:3441-6. 2010
    ..Exposure of rat hepatocytes to insulin produced a 25-fold increase in SREBP-1c mRNA and a 95% decrease in PEPCK mRNA...
  38. ncbi Hepatocyte apoptosis and fas expression are prominent features of human nonalcoholic steatohepatitis
    Ariel E Feldstein
    Division of Gastroenterology and Hepatology, Mayo Clinic and Foundation, 200 First Street SW, Rochester, Minnesota 55905 USA
    Gastroenterology 125:437-43. 2003
    ..Thus, the aims of this study were to quantify hepatocyte apoptosis in NASH, correlate it with disease severity, and identify possible mechanisms of apoptosis induction...
  39. ncbi The human hepatoma HepaRG cells: a highly differentiated model for studies of liver metabolism and toxicity of xenobiotics
    Andre Guillouzo
    INSERM U620, IFR 140, Universite de Rennes1, Rennes, France
    Chem Biol Interact 168:66-73. 2007
    Although they have several important limitations primary human hepatocytes still represent the in vitro gold standard model for xenobiotic metabolism and toxicity studies...
  40. ncbi Fusion of bone-marrow-derived cells with Purkinje neurons, cardiomyocytes and hepatocytes
    Manuel Alvarez-Dolado
    Department of Neurological Surgery, University of California at San Francisco, San Francisco, California 94143 0520, USA
    Nature 425:968-73. 2003
    ..Furthermore, bone marrow transplantation demonstrates that BMDCs fuse in vivo with hepatocytes in liver, Purkinje neurons in the brain and cardiac muscle in the heart, resulting in the formation of ..
  41. ncbi Interleukin 22 (IL-22) plays a protective role in T cell-mediated murine hepatitis: IL-22 is a survival factor for hepatocytes via STAT3 activation
    Svetlana Radaeva
    Section on Liver Biology, Laboratory of Physiologic Studies, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20892, USA
    Hepatology 39:1332-42. 2004
    ..The IL-22 receptor is normally expressed at high levels by hepatocytes and further induced after ConA injection...
  42. ncbi Suppressor of cytokine signaling-3 (SOCS-3), a potential mediator of interleukin-6-dependent insulin resistance in hepatocytes
    Joseph J Senn
    Department of Pathology and Laboratory Medicine, University of Rochester School of Medicine and Dentistry, New York 14642, USA
    J Biol Chem 278:13740-6. 2003
    ..We recently demonstrated that IL-6 inhibits insulin signaling in hepatocytes (Senn, J. J., Klover, P. J., Nowak, I. A., and Mooney, R. A. (2002) Diabetes 51, 3391-3399)...
  43. pmc Fatty acid and endotoxin activate inflammasomes in mouse hepatocytes that release danger signals to stimulate immune cells
    Timea Csak
    Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA
    Hepatology 54:133-44. 2011
    ..We demonstrate for the first time that inflammasome activation occurs in isolated hepatocytes in steatohepatitis...
  44. ncbi Hepatotoxicity and mechanism of action of haloalkanes: carbon tetrachloride as a toxicological model
    Lutz W D Weber
    Institute of Toxicology, GSF National Research Center for Environment and Health, Munich, P O Box 1129, D 85758 Neuherberg FRG
    Crit Rev Toxicol 33:105-36. 2003
    ..Mixed halogenated methanes and ethanes, found as so-called disinfection byproducts at low concentration in drinking water, elicit symptoms of toxicity very similar to carbon tetrachloride, including carcinogenicity...
  45. ncbi Insulin-regulated hepatic gluconeogenesis through FOXO1-PGC-1alpha interaction
    Pere Puigserver
    Dana Farber Cancer Institute and Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Nature 423:550-5. 2003
    ..but co-expression of a mutant allele of FOXO1 insensitive to insulin completely reverses this suppression in hepatocytes or transgenic mice...
  46. pmc Frequent aneuploidy among normal human hepatocytes
    Andrew W Duncan
    Oregon Stem Cell Center, Papé Family Pediatric Research Institute, Oregon Health and Science University, Portland, Oregon, USA
    Gastroenterology 142:25-8. 2012
    Murine hepatocytes become polyploid and then undergo ploidy reversal and become aneuploid in a dynamic process called the ploidy conveyor...
  47. pmc Metabolomic profile of hepatitis C virus-infected hepatocytes
    Barbara Roe
    Centre for Research in Infectious Diseases, School of Medicine and Medical Science, University College Dublin, Belfield, Dublin, Ireland
    PLoS ONE 6:e23641. 2011
    ..These results highlight a number of previously unreported metabolic interactions and give a more in depth insight into the effect HCV has on host cell biochemical processes...
  48. pmc Human hepatic stem cells from fetal and postnatal donors
    Eva Schmelzer
    Department of Cell and Molecular Physiology, School of Medicine, University of North Carolina, Chapel Hill, NC 27599, USA
    J Exp Med 204:1973-87. 2007
    ..Transplantation of freshly isolated EpCAM+ cells or of hHpSCs expanded in culture into NOD/SCID mice results in mature liver tissue expressing human-specific proteins. The hHpSCs are candidates for liver cell therapies...
  49. ncbi Fibroblasts derive from hepatocytes in liver fibrosis via epithelial to mesenchymal transition
    Michael Zeisberg
    Division of Matrix Biology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachussetts 02215, USA
    J Biol Chem 282:23337-47. 2007
    ..The role of adult hepatocytes as contributors to the accumulation of fibroblasts in the fibrotic liver is yet undetermined...
  50. ncbi Cyclosporin A suppresses replication of hepatitis C virus genome in cultured hepatocytes
    Koichi Watashi
    Laboratory of Human Tumor Viruses, Department of Viral Oncology, Institute for Virus Research, Kyoto University, Kyoto, Japan
    Hepatology 38:1282-8. 2003
    ..This anti-HCV activity of CsA appeared to be independent of its immunosuppressive function. In conclusion, our results suggest that CsA may represent a new approach for the development of anti-HCV therapy...
  51. ncbi Obesity affects the liver - the link between adipocytes and hepatocytes
    Alexander Wree
    Department of Gastroenterology and Hepatology, University of Duisburg Essen, University Clinic Essen, Essen, Germany
    Digestion 83:124-33. 2011
    ..Indeed, toxic FFAs can activate the intrinsic apoptosis pathway in hepatocytes via c-Jun N-terminal kinase (JNK)...
  52. pmc Comparing signaling networks between normal and transformed hepatocytes using discrete logical models
    Julio Saez-Rodriguez
    Center for Cell Decision Processes, Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA
    Cancer Res 71:5400-11. 2011
    ..by training a literature-based prior knowledge network against biochemical data obtained from primary human hepatocytes and 4 hepatocellular carcinoma cell lines exposed to combinations of cytokines and small-molecule kinase ..
  53. pmc CD81 is required for hepatitis C virus glycoprotein-mediated viral infection
    Jie Zhang
    Center for the Study of Hepatitis C, Laboratory of Virology and Infectious Diseases, The Rockefeller University, New York, New York 10021, USA
    J Virol 78:1448-55. 2004
    ..These data suggest a functional role for CD81 as a coreceptor for HCV glycoprotein-dependent viral cell entry...
  54. pmc Direct lineage conversion of terminally differentiated hepatocytes to functional neurons
    Samuele Marro
    Institute for Stem Cell Biology and Regenerative Medicine and Department of Pathology, Stanford University School of Medicine, CA 94305, USA
    Cell Stem Cell 9:374-82. 2011
    ..Here, we demonstrate that terminally differentiated hepatocytes can be directly converted into functional iN cells...
  55. pmc CD81 and claudin 1 coreceptor association: role in hepatitis C virus entry
    Helen J Harris
    University of Birmingham, Division of Infection and Immunity, Institute for Biomedical Research, Vincent Dr, Birmingham B15 2TT, United Kingdom
    J Virol 82:5007-20. 2008
    ..the receptors are uniquely expressed within the liver, leading us to hypothesize that their organization within hepatocytes may explain receptor activity...
  56. ncbi Hepatitis C virus entry into hepatocytes: molecular mechanisms and targets for antiviral therapies
    Mirjam B Zeisel
    INSERM, U748, Strasbourg, France
    J Hepatol 54:566-76. 2011
    ..This review summarizes the current knowledge about the molecular mechanisms of HCV entry into hepatocytes, highlights novel targets and reviews the current preclinical and clinical development of compounds targeting ..
  57. pmc Tissue-specific expression of betaKlotho and fibroblast growth factor (FGF) receptor isoforms determines metabolic activity of FGF19 and FGF21
    Hiroshi Kurosu
    Departments of Pathology and Molecular Biology, University of Texas Southwestern Medical Center at Dallas, 6000 Harry Hines Boulevard, Dallas, TX 75390, USA
    J Biol Chem 282:26687-95. 2007
    ..Accordingly, FGF19, but not FGF21, activates FGF signaling in hepatocytes that primarily express FGFR4 and reduces transcription of CYP7A1 that encodes the rate-limiting enzyme for bile ..
  58. ncbi A crucial function of PDGF in TGF-beta-mediated cancer progression of hepatocytes
    J Gotzmann
    Department of Medicine I, Division Institute of Cancer Research, Medical University of Vienna, Vienna, Austria
    Oncogene 25:3170-85. 2006
    Polarized hepatocytes expressing hyperactive Ha-Ras adopt an invasive and metastatic phenotype in cooperation with transforming growth factor (TGF)-beta...
  59. ncbi Efficient generation of hepatocyte-like cells from human induced pluripotent stem cells
    Zhihua Song
    The MOE Key Laboratory of Cell Proliferation and Differentiation, Department of Cell Biology, College of Life Sciences, Box 38, Peking University, Beijing 100871, China
    Cell Res 19:1233-42. 2009
    ..iPS cell-derived cells were monitored and compared with that of differentiated human ES cells and primary human hepatocytes. Approximately 60% of the differentiated human iPS cells at day 7 expressed hepatic markers alpha fetoprotein ..
  60. ncbi Inflammatory pathways in liver homeostasis and liver injury
    Frank Tacke
    Medical Clinic III, RWTH University Hospital Aachen, Pauwelsstrasse 30, 52074, Aachen, Germany
    Clin Rev Allergy Immunol 36:4-12. 2009
    ..the gastrointestinal tract through the sinusoids, and its cellular composition, comprising metabolically active hepatocytes, nonhepatocytic parenchymal cells, and various immune cell populations...
  61. pmc High mobility group box 1 release from hepatocytes during ischemia and reperfusion injury is mediated by decreased histone deacetylase activity
    John Evankovich
    Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA
    J Biol Chem 285:39888-97. 2010
    ..However, mechanisms governing its release by parenchymal cells such as hepatocytes are unknown...
  62. ncbi Efficient differentiation of functional hepatocytes from human embryonic stem cells
    Sadhana Agarwal
    Advanced Cell Technology, 381 Plantation Street, Worcester, Massachusetts 01605, USA
    Stem Cells 26:1117-27. 2008
    ..Current protocols for generating hepatocytes from hESCs are hampered by inefficient differentiation procedures that lead to low yields and large cellular ..
  63. pmc Robust expansion of human hepatocytes in Fah-/-/Rag2-/-/Il2rg-/- mice
    Hisaya Azuma
    Oregon Stem Cell Center, Oregon Health and Science University, Portland, Oregon 97239, USA
    Nat Biotechnol 25:903-10. 2007
    Mice that could be highly repopulated with human hepatocytes would have many potential uses in drug development and research applications...
  64. ncbi A regulatory cascade of the nuclear receptors FXR, SHP-1, and LRH-1 represses bile acid biosynthesis
    B Goodwin
    Department of Molecular Endocrinology, Glaxo Wellcome Research and Development, Research Triangle Park, North Carolina 27709, USA
    Mol Cell 6:517-26. 2000
    ..This bile acid-activated regulatory cascade provides a molecular basis for the coordinate suppression of CYP7A1 and other genes involved in bile acid biosynthesis...
  65. ncbi Human mesenchymal stem cells xenografted directly to rat liver are differentiated into human hepatocytes without fusion
    Yasushi Sato
    Fourth Department of Internal Medicine, Sapporo Medical University, School of Medicine, Sapporo, 060 8543, Japan
    Blood 106:756-63. 2005
    ..the present study, to elucidate which cellular components of human bone marrow more potently differentiate into hepatocytes, we fractionated human bone marrow cells into mesenchymal stem cells (MSCs), CD34+ cells, and non-MSCs/CD34- ..
  66. pmc Hepatocytes do not undergo epithelial-mesenchymal transition in liver fibrosis in mice
    Kojiro Taura
    Department of Medicine, University of California, San Diego, School of Medicine, La Jolla, CA, USA
    Hepatology 51:1027-36. 2010
    The origin of fibrogenic cells in liver fibrosis remains controversial. We assessed the emerging concept that hepatocytes contribute to production of extracellular matrix (ECM) in liver fibrosis through epithelial-mesenchymal transition (..
  67. pmc Stem cell therapy for liver disease: parameters governing the success of using bone marrow mesenchymal stem cells
    Tom K Kuo
    Institute of Biopharmaceutical Science, National Yang Ming University, Taipei, Taiwan
    Gastroenterology 134:2111-21, 2121.e1-3. 2008
    ..The aim of this study was to critically analyze the various parameters governing the success of bone marrow-derived mesenchymal stem cell-based therapy for treatment of liver diseases...
  68. ncbi Directed differentiation of human embryonic stem cells into functional hepatic cells
    Jun Cai
    Key Laboratory of Cell Proliferation and Differentiation of the Ministry of Education, College of Life Sciences, Peking University, Beijing, China
    Hepatology 45:1229-39. 2007
    ..Furthermore, these cells exhibited functions associated with mature hepatocytes including albumin secretion, glycogen storage, indocyanine green, and low-density lipoprotein uptake, and ..
  69. ncbi Role of STAT-3 in regulation of hepatic gluconeogenic genes and carbohydrate metabolism in vivo
    Hiroshi Inoue
    Department of Clinical Molecular Medicine, Division of Diabetes and Digestive and Kidney Diseases, Kobe University Graduate School of Medicine, Kobe 650 0017, Japan
    Nat Med 10:168-74. 2004
    ..Overexpression of STAT-3 in cultured hepatocytes inhibited gluconeogenic gene expression independently of peroxisome proliferator-activated receptor-gamma ..
  70. pmc Interferon-lambda (IFN-λ) induces signal transduction and gene expression in human hepatocytes, but not in lymphocytes or monocytes
    Harold Dickensheets
    Division of Therapeutic Proteins, Center for Drug Evaluation and Research, U S Food and Drug Administration, 29 Lincoln Dr, Bethesda, MD 20892, USA
    J Leukoc Biol 93:377-85. 2013
    ..compared the ability of IFN-α and IFN-λ to induce signal transduction and gene expression in primary human hepatocytes, PBLs, and monocytes...
  71. ncbi Serum retinol binding protein 4 contributes to insulin resistance in obesity and type 2 diabetes
    Qin Yang
    Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA
    Nature 436:356-62. 2005
    ..Thus, RBP4 is an adipocyte-derived 'signal' that may contribute to the pathogenesis of type 2 diabetes. Lowering RBP4 could be a new strategy for treating type 2 diabetes...
  72. ncbi Liver progenitor cells yield functional hepatocytes in response to chronic liver injury in mice
    Regina Español-Suñer
    Laboratory of Hepato Gastroenterology, Institut de Recherche Expérimentale et Clinique, Universite Catholique de Louvain, Brussels, Belgium
    Gastroenterology 143:1564-1575.e7. 2012
    Self-renewal of mature hepatocytes promotes homeostasis and regeneration of adult liver...
  73. ncbi Generation of metabolically functioning hepatocytes from human pluripotent stem cells by FOXA2 and HNF1α transduction
    Kazuo Takayama
    Laboratory of Biochemistry and Molecular Biology, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka 565 0871, Japan
    J Hepatol 57:628-36. 2012
  74. ncbi Organogenesis and development of the liver
    Karim Si-Tayeb
    Department of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA
    Dev Cell 18:175-89. 2010
    ..Here, we review the basic molecular mechanisms that control the formation of the liver as an organ...
  75. pmc Visualisation and quantitative analysis of the rodent malaria liver stage by real time imaging
    Ivo H J Ploemen
    Department of Medical Microbiology, Radboud University Nijmegen Medical Centre RUNMC, Nijmegen, The Netherlands
    PLoS ONE 4:e7881. 2009
    ..The reporter-parasite based quantification in cultured hepatocytes by real-time imaging or using a microplate reader correlates very well with established quantitative RT-PCR ..
  76. pmc Targeted delivery of RNAi therapeutics with endogenous and exogenous ligand-based mechanisms
    Akin Akinc
    Alnylam Pharmaceuticals, Cambridge, Massachusetts, USA
    Mol Ther 18:1357-64. 2010
    Lipid nanoparticles (LNPs) have proven to be highly efficient carriers of short-interfering RNAs (siRNAs) to hepatocytes in vivo; however, the precise mechanism by which this efficient delivery occurs has yet to be elucidated...
  77. pmc Orphan nuclear receptor estrogen-related receptor γ (ERRγ) is key regulator of hepatic gluconeogenesis
    Don Kyu Kim
    National Creative Research Initiatives Center for Nuclear Receptor Signals, School of Biological Sciences and Technology, Chonnam National University, Gwangju 500 757, Republic of Korea
    J Biol Chem 287:21628-39. 2012
    ..Overexpression of ERRγ induced Pck1 and G6PC gene expression and glucose production in primary hepatocytes, whereas abolition of ERRγ gene expression attenuated forskolin-mediated induction of gluconeogenic gene ..
  78. pmc Secreted PCSK9 decreases the number of LDL receptors in hepatocytes and in livers of parabiotic mice
    Thomas A Lagace
    Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA
    J Clin Invest 116:2995-3005. 2006
    ..Purified PCSK9 had no effect on cell-surface LDLRs in hepatocytes lacking autosomal recessive hypercholesterolemia (ARH), an adaptor protein required for endocytosis of the ..
  79. pmc Productive hepatitis C virus infection of stem cell-derived hepatocytes reveals a critical transition to viral permissiveness during differentiation
    Xianfang Wu
    Department of Biological Science, Florida State University, Tallahassee, Florida, United States of America
    PLoS Pathog 8:e1002617. 2012
    Primary human hepatocytes isolated from patient biopsies represent the most physiologically relevant cell culture model for hepatitis C virus (HCV) infection, but these primary cells are not readily accessible, display individual ..
  80. pmc Mature hepatocytes exhibit unexpected plasticity by direct dedifferentiation into liver progenitor cells in culture
    Yixin Chen
    Department of Medicine, University of Minnesota Medical School, Minneapolis, MN 55455, USA
    Hepatology 55:563-74. 2012
    ..cells from the adult liver, their exact origin has not been clearly defined; and the role played by mature hepatocytes as direct contributors to the hepatic progenitor cell pool has remained largely unknown...
  81. pmc Hepatitis B virus X protein downregulates expression of the miR-16 family in malignant hepatocytes in vitro
    G Wu
    Department of Hepatobiliary Surgery, Sun Yat Sen Memorial Hospital, Sun Yat Sen University, 107 Yanjiang West Road, Guangzhou 510120, People s Republic of China
    Br J Cancer 105:146-53. 2011
    ..In this study, we showed that HBx altered the expression of microRNAs (miRNAs) to promote proliferation and transformation in malignant hepatocytes in vitro.
  82. ncbi Adipose tissue-derived mesenchymal stem cells as a source of human hepatocytes
    Agnieszka Banas
    Section for Studies on Metastasis, National Cancer Center Research Institute 1 1, Tokyo, Japan
    Hepatology 46:219-28. 2007
    Recent observations indicate that several stem cells can differentiate into hepatocytes; thus, cell-based therapy is a potential alternative to liver transplantation...
  83. ncbi PPARalpha is a key regulator of hepatic FGF21
    Thomas Lundåsen
    Center for Endocrinology, Metabolism, and Diabetes, Department of Medicine, M63, Karolinska Institutet, Karolinska University Hospital, Huddinge, SE 141 86 Stockholm, Sweden
    Biochem Biophys Res Commun 360:437-40. 2007
    ..for FGF21 expression also in human liver was shown by Wy-14,643 induction of FGF21 mRNA in human primary hepatocytes, and PPARalpha response elements were identified in both the human and mouse FGF21 promoters...
  84. pmc Bats carry pathogenic hepadnaviruses antigenically related to hepatitis B virus and capable of infecting human hepatocytes
    Jan Felix Drexler
    Institute of Virology, University of Bonn Medical Centre, 53127 Bonn, Germany
    Proc Natl Acad Sci U S A 110:16151-6. 2013
    ..Infected livers showed histopathologic changes compatible with hepatitis. Human hepatocytes transfected with all three bat viruses cross-reacted with sera against the HBV core protein, concordant with ..
  85. pmc Multipotent adult progenitor cells from bone marrow differentiate into functional hepatocyte-like cells
    Robert E Schwartz
    Stem Cell Institute, University of Minnesota, Minneapolis 55455, USA
    J Clin Invest 109:1291-302. 2002
    ..These cells also acquired functional characteristics of hepatocytes: they secreted urea and albumin, had phenobarbital-inducible cytochrome p450, could take up LDL, and stored ..
  86. pmc The logic of EGFR/ErbB signaling: theoretical properties and analysis of high-throughput data
    Regina Samaga
    Max Planck Institute for Dynamics of Complex Technical Systems, Magdeburg, Germany
    PLoS Comput Biol 5:e1000438. 2009
    ..By employing these techniques for phospho-proteomic data from primary hepatocytes and the HepG2 cell line, we demonstrate that our approach enables one to uncover inconsistencies between ..
  87. ncbi Therapeutic effect of transplanting HGF-treated bone marrow mesenchymal cells into CCl4-injured rats
    Suguru Oyagi
    Graduate School of Pharmaceutical Sciences, Osaka University, 1 6 Yamada oka, Suita, Osaka 565 0871 Japan
    J Hepatol 44:742-8. 2006
    ..Pluripotent bone marrow stem cells can differentiate into hepatocytes, but few reports address the therapeutic effect of transplanting these stem cells into damaged liver in vivo...
  88. ncbi Hepatitis B virus X protein is essential to initiate and maintain virus replication after infection
    Julie Lucifora
    Institute of Virology, Technische Universität München Helmholtz Zentrum München, Trogerstrasse, 30, 81675 Munich, Germany
    J Hepatol 55:996-1003. 2011
    ..The molecular biology of hepatitis B virus (HBV) has been extensively studied but the exact role of the hepatitis B X protein (HBx) in the context of natural HBV infections remains unknown...
  89. pmc Hepatocyte growth factor/c-met signaling pathway is required for efficient liver regeneration and repair
    Chang Goo Huh
    Laboratory of Experimental Carcinogenesis, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 37 Convent Drive MSC 4262, Building 37, Room 4146A, Bethesda, MD 20892 4262, USA
    Proc Natl Acad Sci U S A 101:4477-82. 2004
    ..Mice lacking c-met gene in hepatocytes were hypersensitive to Fas-induced apoptosis...
  90. ncbi Polyploidization of liver cells
    Séverine Celton-Morizur
    Institut Cochin, Universite Paris Descartes, CNRS, UMR 8104, INSERM U567, Paris, France
    Adv Exp Med Biol 676:123-35. 2010
    ..growth, the liver parenchyma undergoes dramatic changes characterized by gradual polyploidization during which hepatocytes of several ploidy classes emerge as a result of modified cell-division cycles...
  91. pmc Molecular mechanisms of lipotoxicity in nonalcoholic fatty liver disease
    Harmeet Malhi
    Miles and Shirley Fiterman Center for Digestive Diseases, Mayo Clinic, College of Medicine, Rochester, Minnesota 55905, USA
    Semin Liver Dis 28:360-9. 2008
    ..Understanding the molecular mediators of liver injury should promote development of mechanism-based therapeutic interventions...
  92. pmc Inhibition of core gene of HCV 3a genotype using synthetic and vector derived siRNAs
    Saba Khaliq
    Applied and Functional Genomics Laboratory, National Center of Excellence in Molecular Biology, University of Punjab, Lahore 53700, Pakistan
    Virol J 7:318. 2010
    ..Due to the limited efficiency of current therapy, RNA interference (RNAi) a novel regulatory and powerful silencing approach for molecular therapeutics through a sequence-specific RNA degradation process represents an alternative option...
  93. ncbi Differentiation of human adipose stromal cells into hepatic lineage in vitro and in vivo
    Min Jeong Seo
    Department of Physiology, College of Medicine, Pusan National University, Pusan 602 739, Republic of Korea
    Biochem Biophys Res Commun 328:258-64. 2005
    ..cells, and hepatic stem cells in liver have been known as a useful source that can induce to differentiate into hepatocytes. In this study, we examined whether human adipose tissue-derived stromal cells (hADSC) can differentiate into ..
  94. ncbi c-Jun N-terminal kinase plays a major role in murine acetaminophen hepatotoxicity
    Basuki K Gunawan
    Research Center for Liver Disease, Keck School of Medicine, University of Southern California, Los Angeles, 90033, USA
    Gastroenterology 131:165-78. 2006
    In searching for effects of acetaminophen (APAP) on hepatocytes downstream of its metabolism that may participate in hepatotoxicity, we examined the role of stress kinases.
  95. pmc Establishment of B-cell lymphoma cell lines persistently infected with hepatitis C virus in vivo and in vitro: the apoptotic effects of virus infection
    Vicky M H Sung
    Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, California 90033, USA
    J Virol 77:2134-46. 2003
    ..13 to 1.15 g/ml in sucrose and could infect primary human hepatocytes, peripheral blood mononuclear cells (PBMCs), and an established B-cell line (Raji cells) in vitro...
  96. pmc The nuclear factor HMGB1 mediates hepatic injury after murine liver ischemia-reperfusion
    Allan Tsung
    Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15213, USA
    J Exp Med 201:1135-43. 2005
    ..Together, these results demonstrate that HMGB1 is an early mediator of injury and inflammation in liver I/R and implicates TLR4 as one of the receptors that is involved in the process...
  97. ncbi Regulation of tissue homeostasis by NF-kappaB signalling: implications for inflammatory diseases
    Manolis Pasparakis
    Institute of Genetics, Centre for Molecular Medicine CMMC, and Cologne Excellence Cluster on Cellular Stress Responses in Aging associated Diseases CECAD, University of Cologne, Zulpicher Strasse 47, 50674 Cologne, Germany
    Nat Rev Immunol 9:778-88. 2009
    ..This Review discusses the mechanisms by which NF-kappaB activity in non-immune cells regulates tissue immune homeostasis and prevents the pathogenesis of inflammatory diseases...
  98. pmc Stem cells and liver regeneration
    Andrew W Duncan
    Oregon Stem Cell Center, Oregon Health and Science University, Portland, Oregon 97239 3098, USA
    Gastroenterology 137:466-81. 2009
    ..This review will consider liver stem cells in the context of each definition...
  99. pmc Direct infection and replication of naturally occurring hepatitis C virus genotypes 1, 2, 3 and 4 in normal human hepatocyte cultures
    Martina Buck
    Department of Medicine and Moores Cancer Center, University of California, La Jolla, California, United States of America
    PLoS ONE 3:e2660. 2008
    ..the HCV life cycle is only partially understood because it has not been possible to infect normal human hepatocytes in culture...
  100. ncbi Swelling of hepatocytes injured by oxidative stress suggests pathological changes related to macromolecular crowding
    U Del Monte
    Institute of General Pathology, University of Milano, Via L Mangiagalli 31, 20133 Milan, Italy
    Med Hypotheses 64:818-25. 2005
    ..Models and techniques apt to investigate this problem experimentally are suggested...
  101. ncbi Hepatitis C virus triggers apoptosis of a newly developed hepatoma cell line through antiviral defense system
    Haizhen Zhu
    Department of Pathology, Immunology, and Laboratory Medicine, University of Florida College of Medicine, Gainesville, Florida, USA
    Gastroenterology 133:1649-59. 2007
    ..However, the interaction between HCV and hepatocyte innate antiviral defense systems is not understood. The aim of this study was to examine how human hepatocytes respond to HCV infection.

Research Grants74

  1. Mice Humanized with Hepatocytes and iPS Cells from Patients with Metabolic Diseas
    Stephen C Strom; Fiscal Year: 2010
    ..hypothesis, that the best models for human metabolic liver disease are those created from the affected human hepatocytes. Thus, we propose to" humanize" the liver of FRG mice by transplantation of affected human hepatocytes to ..
  2. Pathogenesis and Treatment of Liver Disease in Transaldolase Deficiency
    Andras Perl; Fiscal Year: 2013
    ..TAL-/- hepatocytes were resistant to CD95/Fas-mediated apoptosis in vitro and in vivo...
  3. Med1 in Liver Metabolism, Regeneration and Cancer
    Janardan K Reddy; Fiscal Year: 2013
    ..Med1 also controls liver regeneration and the development of hepatocellular carcinoma (HCC), in that hepatocytes lacking Med1 fail to regenerate and fail to give rise to liver tumors...
  4. Transgenesis and Xenotransplantation
    Jorge A Piedrahita; Fiscal Year: 2013
    ..Aim 3. To develop a transgenic pig that will facilitate engraftment and proliferation of human hepatocytes. Aim 3a will focus on generation of a transgenic swine carrying Cre-ERT2, a tamoxifen inducible Cre, driven by ..
    Lisa M Salati; Fiscal Year: 2012
    ..acids regulate gene expression, we discovered that the rate of RNA splicing is inhibited in liver and primary hepatocytes by dietary polyunsaturated fat and by arachidonic acid, respectively...
  6. Ubiquitous pollutant acrolein inhibits IFN?? antiviral signaling: relevance to HC
    Swati Joshi-Barve; Fiscal Year: 2013
    ..IFN1 therapy outcomes by inhibiting or disrupting IFN1 mediated signaling and antiviral gene expression in hepatocytes, and that high acrolein exposure (environmental and/or endogenous) will correlate with poor IFN1 response in ..
  7. Regulation of Cell Signaling by Human Biliverdin Reductase
    Mahin D Maines; Fiscal Year: 2013
    ..Specific Aim 3 will evaluate in primary rat hepatocytes and in ex vivo perfused rat liver protection by hBVR peptides against interferon-3-mediated toxicity...
  8. PUFA Synthesis and the Control of Hepatic Metabolism
    Donald B Jump; Fiscal Year: 2013
    ..Using cultured hepatocytes and obese-diabetic mice, Aim 1 will define how endogenously generated and exogenously supplied PUFA control ..
  9. Iron-Induced Changes in Liver That Predispose to Malignancy
    Harriet C Isom; Fiscal Year: 2010
    ..HCC is a slow process that occurs in the setting of liver cell injury. Hepatocytes are triggered to replicate. Oxidative stress is induced resulting in oxidative damage to DNA...
  10. Regulation of Hepatic SphK2 by Bile Acids: Effects on Lipid Metabolism
    HUIPING ROSE ZHOU; Fiscal Year: 2013
    ..activate the S1P receptor 2 (S1P2), which further activates the downstream ERK1/2 and AKT signaling pathways in hepatocytes. We recently discovered that in SphK2-/- mice the mRNA levels of key transcriptional factors and key enzymes ..
  11. Potential Mechanisms of Glucagon-like peptide-1 in Fatty Liver Disease
    Frank A Anania; Fiscal Year: 2010
    ..resistance is the primary pathophysiologic problem that results in a net accumulation of triglycerides in hepatocytes. At present there is limited therapy for fatty liver disease...
  12. Role of GDNF in the regulation of hepatic steatosis
    SHANTHI K SRINIVASAN; Fiscal Year: 2013
    ..GFAP promoter (GDNF-tg) (ii) GDNF (expressed in glia) and its receptor GFR-1a are expressed in human and murine hepatocytes (iii) GDNF-tg mice demonstrate enhanced energy utilization assessed by indirect calorimetry, (iv) compared to ..
  13. Functional characters of non-coding RNAs in alcoholic liver injury
    Fanyin Meng; Fiscal Year: 2013
    ..identify the functional ethanol-dependent miRNAs involved in cell survival in human hepatic stellate cells, hepatocytes and cholangiocytes...
  14. Alcohol, Proteasome Dysfunction in Liver Injury
    Craig J McClain; Fiscal Year: 2013
    ..Our preliminary data demonstrate that inhibition of 26S proteasome function can sensitize hepatocytes to TNF cytotoxicity, and higher doses of proteasome inhibitors directly induce hepatocyte death...
  15. Novel SCID rat models for human cell transplantation studies
    Joseph C Ruiz; Fiscal Year: 2010
    ..In Phase II, we will transplant primary human cells (e.g., hepatocytes) into the transgenic animals, in proof-of-principal studies to demonstrate the long-term viability and function ..
    John J Lemasters; Fiscal Year: 2012
    ..of intravital multiphoton microscopy to visualize parameter- indicating fluorophores inside individual hepatocytes and their organelles in liver grafts of living rats and mice...
  17. Role of Platelet derived growth factor receptor-a in Liver Patho-biology
    SATDARSHAN SINGH MONGA; Fiscal Year: 2013
    ..Specifically, hepatoblasts and immature hepatocytes displayed high expression at early hepatic developmental stages that coincide with ongoing cell proliferation ..
  18. Histamine modulation of biliary proliferation and damage
    Heather L Francis; Fiscal Year: 2013
    ..i) hepatic distribution/expression of HDC in liver sections and purified liver cells including cholangiocytes, hepatocytes and vascular endothelial cells;and (ii) in vivo effects of the modulation of HDC expression on biliary growth/..
  19. Hepatic Steatosis and ER Stress-Inducible Transcription Factor CREBH
    Kezhong Zhang; Fiscal Year: 2013
    ..protein beta (C/EBP2) and peroxisome proliferator- activated receptor gamma (PPAR3), in liver hepatocytes under the metabolic stress...
  20. Role of Membrane Modifications in the Bioactivities of Conjugated Linoleic Acids
    Papasani V Subbaiah; Fiscal Year: 2013
    ..We will first determine the incorporation profiles of different CLA isomers into membranes of cultured hepatocytes, adipocytes, and myocytes of human and mouse origins...
  21. Hepatitis B virus replication and DDB1
    Betty L Slagle; Fiscal Year: 2013
    ..Human liver chimeric mice, in which human hepatocytes are engrafted into immunodeficient mice, provide the best, most biologically relevant model system to ..
  22. Mechanism(s) of Hepatocyte Transformation by the Hepatitis B Virus X Protein
    Ourania M Andrisani; Fiscal Year: 2013
    ..In turn, Plk1 mediates checkpoint adaptation, generating partial polyploidy in non- transformed pX-expressing hepatocytes. Significantly, inhibition of Plk1 suppresses pX-mediated transformation...
  23. Lipid Transport, Bile Acid Synthesis, and Cholesterol Homeostasis
    William M Pandak; Fiscal Year: 2013
    ..NAFLD) is a disorder of hepatic lipid homeostasis in which both cholesterol and triglycerides accumulate in hepatocytes. A fraction of patients with NAFLD progress to liver cell necrosis, inflammation, and progressive fibrosis...
  24. Mechanisms of Neutrophil-induced Liver Toxicity
    HARTMUT W JAESCHKE; Fiscal Year: 2012
    ..Reactive oxygen species (ROS) generated by these inflammatory cells diffuse into hepatocytes and trigger an intracellular oxidant stress, which ultimately causes necrotic cell death...
  25. Mechanistic Characterization and Genetic Analysis of Systemic Iron Homeostasis
    Xin Du; Fiscal Year: 2011
    ..Moreover, our data revealed that TMPRSS6 is an essential component of the "low iron" sensing apparatus in hepatocytes. Specifically: 1...
  26. Use of umbilical cord as a unique stem cell source for tissue regeneration
    Xiao Dong Chen; Fiscal Year: 2013
    ..lineage, including osteoblasts, adipocytes, chondroblasts and cardiomyocytes (mesoderm), nerve (ectoderm) and hepatocytes (endoderm)...
  27. The Role of H6PDH and 11beta-HSD1 in Type 2 Diabetes and Obesity
    Yanjun Liu; Fiscal Year: 2013
    ..of H6PDH to regulation of 12-HSD1 amplifying GC regeneration by using siRNA technology in intact mouse hepatocytes and adipocytes...
  28. Regulation of Hepatic Lipid and Glucose Metabolism by PC-TP/StarD2
    David E Cohen; Fiscal Year: 2013
    ..Aim 1, a newly developed small molecule inhibitor of PC-TP, as well as Pctp-/- and Them2-/- mice and cultured hepatocytes will be used to examine whether a complex of PC-TP and Them2 limits insulin signaling and thereby promotes ..
  29. Deriving hepatocytes from disease specific iPS to treat metabolic liver disorders
    Namita Roy-Chowdhury; Fiscal Year: 2013
    ..UGT1A1) deficiency can be corrected genetically, and then manipulated in culture to generate hepatocytes expressing active UGT1A1...
  30. Modifiers of hepcidin expression as new therapies for iron overload
    PAULA GOODMAN FRAENKEL; Fiscal Year: 2013
    ..the phytoestrogen, genistein, results in increased hepcidin transcript levels in zebrafish embryos and in human hepatocytes. We propose to screen for additional small molecules that regulate hepcidin expression by conducting a chemical ..
  31. Effect of HIV protease inhibitor on alcohol induced ER stress and liver injury.
    Cheng Ji; Fiscal Year: 2013
    ..We propose to explore the HIV PI-induced ER stress response in both primary mouse and human hepatocytes and to investigate in vivo its interactions with pathogenic effects of alcohol in animals fed alcohol...
  32. Metabolic Crosstalk Between Immune Cells and the Liver in Obesity
    BENJAMIN MANTELL; Fiscal Year: 2012
    ..immune cells on liver metabolism, we will be utilizing a co-culture system which allows us to maintain primary hepatocytes in close proximity to, but preventing direct contact with, mononuclear cells...
  33. Double Humanization of Liver and Blood in Mice
    ELIZABETH MARIE WILSON; Fiscal Year: 2012
    ..In the current human chimeric liver models up to 90% of hepatocytes are of human origin and display all the typical functions of mature human cells...
  34. Sterile Hepatic Inflammation
    Wajahat Zafar Mehal; Fiscal Year: 2012
    ..iii) DNA from apoptotic hepatocytes can activate TLR9 on sinusoidal endothelial cells, and cause liver injury...
  35. Hepatocyte Nox proteins in the pathogenesis of hepatocellular carcinoma
    Jinah Choi; Fiscal Year: 2013
    ..laboratory discovered that hepatocyte NAD(P)H oxidases 1 and 4 (Nox1 and Nox4) are prominent sources of ROS in hepatocytes producing infectious HCV as well as in the HCV-infected human liver...
  36. Role of Heat Shock Transcription Factor Hsf1 in Tumorigenesis
    Nahid F Mivechi; Fiscal Year: 2013
    ..g., hepatocytes or macrophages), and (2) examine HCC development under conditions where Hsf1 is constitutively active due to ..
  37. Role of inflammation and cellular stress in the pathogenesis of type 2 diabetes
    Liangyou Rui; Fiscal Year: 2013
    ..Deletion of NIK decreased lipogenesis and increased oxidation in hepatocytes. Hepatic NIK was aberrantly activated in obesity;CREB and activated NF- B2 levels were increased in the livers ..
  38. Hepatocarcinogenesis Secondary to Hepatitis C
    Srikanta Dash; Fiscal Year: 2012
    ..Jak-Stat signaling molecules that control the transcription of interferon-inducible genes varies among infected hepatocytes in the liver...
  39. Combination therapies for chronic HBV, liver disease and cancer
    Mark A Feitelson; Fiscal Year: 2012
    ..will assess the pharmacokinetics (PK), antiviral efficacy and toxicity of drug combinations in primary human hepatocytes and in HepG2 cells replicating wild type or selected mutants of HBV (aim 1)...
  40. New pathways regulating bile acid homeostasis and cholestatic liver diseases
    Li Wang; Fiscal Year: 2013
    ..bile flow will cause intrahepatic retention of cytotoxic bile acids, leading to liver injury to bile ducts and hepatocytes, and resulting in cholestatic liver diseases...
  41. mTORC1-dependent regulation of the CycC/CDK8 complex
    Jeffrey E Pessin; Fiscal Year: 2013
    ..of fatty acids and triglycerides and it is the primary effecto of insulin-induced de novo lipogenesis in hepatocytes. Insulin and feeding acutely regulates SREBP-1c transcriptional activity at three distinct levels by 1) ..
  42. Human cytomegalovirus entry into epithelial and endothelial cells
    David C Johnson; Fiscal Year: 2013
    ..infect a very broad spectrum of human cell types including retinal and gut epithelial cells, endothelial cells, hepatocytes, monocyte-macrophages and glial cells...
  43. Phospholipid-Mediated Metabolic Control in Liver and Brown Adipose Tissue
    David E Cohen; Fiscal Year: 2013
    ..Additional mechanistic insights will be gleaned from experiments in cultured primary mouse hepatocytes, as wel as HEK 293T cells in which expression of endogenous Them2 and PC-TP are silenced using siRNAs...
  44. Role of NPC1L1 in regulating energy metabolism, nutrient utilization & weight gai
    Philip N Howles; Fiscal Year: 2010
    ..Aim 1 will also determine if metabolic changes derive from increased activation of specific receptors in hepatocytes due to chronic cholesterol loss...
  45. Lipid Metabolism and Steatosis in Liver
    Amrita Kamat; Fiscal Year: 2013
    ..increases hepatic lipid accumulation in livers of young rodents, whereas inhibition of B-AR signaling in hepatocytes from old rodents reduces cellular lipid accumulation...
  46. Epigenetic Regulation Of Sex-dependent Liver Cancer
    Arlin B Rogers; Fiscal Year: 2012
    ..Liver masculinization is enacted by pulsatile growth hormone from the pituitary. Hepatocytes transduce this signal through Stat5b, which translocates to the nucleus and initiates the male transcription ..
  47. Influence of Heme on Hepatic Cytochrome P450 Turnover
    Maria Almira Correia; Fiscal Year: 2013
    ..Inhibition of heme synthesis in rat or mouse hepatocytes also results in acute heme depletion and consequent autoactivation of hepatic heme-regulated inhibitor HRI eIF2?..
    SHELLY CHI LOO LU; Fiscal Year: 2013
    ..ursodeoxycholic acid (UDCA) and S-adenosylmethionine (SAMe) prevented the fall in GCL subunits mRNA levels in hepatocytes (UDCA and SAMe) during cholestasis, and in macrophages (SAMe) during LPS treatment...
    Maria Almira Correia; Fiscal Year: 2013
    ..In addition, we have also found that gp78- and CHIP- knockdown via RNA-interference in rat hepatocytes results in increased levels of functionally active hepatic P450s...
  50. Role of Polo-like kinase (Plk-1) in Hepatitis B Virus-mediated Hepatocellular Car
    Ourania M Andrisani; Fiscal Year: 2010
    ..Our previous studies have found that in non-transformed hepatocytes, pX induces DNA re-replication, resulting in DNA damage and polyploidy...
    ..We will also explore the ability of other non-renal epithelial cells such as hepatocytes to be reprogrammed by small molecules into renal progenitor cells...
  52. Role of sumoylation in alcoholic liver disease
    Maria Lauda Tomasi; Fiscal Year: 2013
    ..Ethanol treatment of primary mouse hepatocytes leads to increased reactive oxygen species (ROS) and triglyceride production...
  53. Analysis of FIP200 in signal transduction
    Jun Lin Guan; Fiscal Year: 2012
    ..Analysis of FIP200 KO mice as well as isolated MEFs and hepatocytes also suggest a role for FIP200 in the regulation of cell survival and apoptosis...
  54. Human hepatocytes for drug toxicity screening from Cardiac Death Donor livers
    Mark G Clemens; Fiscal Year: 2012
    ..Because of the many species differences between humans and commonly used animal models, testing on human hepatocytes remains the gold standard for drug screening...
  55. Control of liver autophagy by phosphatidic acid signaling
    GILBERT DIPAOLO; Fiscal Year: 2013
    ..e., "macrolipophagy") in hepatocytes and many other cell types...
  56. Aging and Apoptosis
    Brian A Herman; Fiscal Year: 2012
    ..these hypotheses we will undertake the following specific aims: 1) Determine the age-dependent sensitivity of hepatocytes, cortical neurons, mesenchepalic cells and fibroblasts obtained from caspase-2^, caspase-2 liver specific (..
  57. DNA Repair of Endogenous Lesions in Carcinogenesis
    Rabindra Roy; Fiscal Year: 2010
    ..rate-limiting BER enzymes by assessing the effects of metals (copper and iron), hydrogen peroxide, and enals in hepatocytes of LEA and LEG rats and comparing the effects with that observed in tissues obtained from Aim 1;(4) study ..
  58. Heme Oxygenase Enzymes/Carbon Monoxide in Hepatic Dysfunction from hemorrhage
    BRIAN SCOTT ZUCKERBRAUN; Fiscal Year: 2013
    ..Our studies concentrate on the influence of HO enzymes and CO within the liver and hepatocytes, as hepatic injury has been a major area of investigation within our laboratory...
  59. Abnormal Bone Marrow Cells and Diabetic Neuropathy
    Lawrence Chan; Fiscal Year: 2013
    ..In diabetes, the hyperglycemia-induced PI-BMDCs circulate to the liver where they form fusion cells with hepatocytes (Fujimiya et al., 2007)...
  60. Hepatitis C virus and liver fibrogenesis
    Gulam Waris; Fiscal Year: 2010
    ..HCV infected hepatocytes display oxidative stress which may provide a link between HCV infection and activation of TGF-21 that leads to ..
  61. Coronavirus modulation of cellular microRNAs in the liver: role in hepatitis
    Sonia Navas-Martin; Fiscal Year: 2012
    ..coronaviruses to induce hepatitis is virus strain specific, and identified cellular targets in the liver (hepatocytes, endothelial cells, and the resident macrophage Kupffer cells)...
    Itzhak Nissim; Fiscal Year: 2013
    ..will be performed using a rat model of fatty liver and/or MS and various systems, including (a) isolated hepatocytes;(b) a liver perfusion system;(c) isolated mitochondria;and (d) in vivo study...
  63. A Microfluidic-platform Mini-Liver System for Human Liver Biology Studies
    HONGSEOK M NOH; Fiscal Year: 2010
    ..that have limited development of human liver model systems include the difficulty in maintaining differentiated hepatocytes in traditional cell-culture environments and the difficulty in obtaining large numbers of normal human ..
  64. FAH-Deficient Pigs
    Scott L Nyberg; Fiscal Year: 2011
    ..These FAH deficient mice serve as in vivo bioreactors for the robust expansion of normal human hepatocytes. We postulate that scale up of the FAH deficient platform to pigs is possible, and that FAH deficient pigs will ..
    Tarun Patel; Fiscal Year: 1993
    ..preliminary data presented in this application demonstrates that in perfused rat livers and perfused rat hepatocytes, the ability of atriopeptins to elevate cGMP levels and stimulate gluconeogenesis is also regulated by the ..
  66. MR Spectroscopy to Evaluate Liver Repopulation by Transplanted Hepatocytes
    Chandan Guha; Fiscal Year: 2009
    ..However, benefits of this procedure are currently limited by (i) the inability of the transplanted hepatocytes to proliferate in the host liver, and (ii) lack of a noninvasive method to evaluate the repopulation of ..
    Robert Hamilton; Fiscal Year: 1991
    ..the Investigator's abstract): The long-term goals of this research are to determine the mechanisms by which hepatocytes secrete lipoproteins and apolipoproteins...
  68. Screening for Chemicals that Potentiate TRAIL-Induced Apoptosis of Cancer Cells
    DMITRI ROZANOV; Fiscal Year: 2007
    ..apoptosis will be validated in an additional assay to select chemicals that are non-toxic to normal human hepatocytes. Our Specific Aims are: (1) To identify low molecular weight chemicals that can efficiently enhance TRAIL-..
  69. Hepatocyte - Based Therapies of Primary Hyperoxaluria 1
    Namita Roy Chowdhury; Fiscal Year: 2010
    Primary hyperoxaluria type I (PH1) is an autosomal recessive disease caused by excessive oxalate production by hepatocytes due to peroxisomal alanine-glyoxylate aminotransferase (AGT) deficiency, leading to increased conversion of ..
    PAULA DEHN; Fiscal Year: 1990
    ..Primary cultures of mammalian hepatocytes have proved invaluable for studying mechanisms of pharmacotoxicity and exhibit several advantages over freshly ..
    Ronald Tompkins; Fiscal Year: 1991
    The objective is the immobilization of hepatocytes for use in an artificial liver device. Hepatocytes will be isolated by established techniques using collagenase digestion and immobilized in a sodium alginate gel matrix...
    Stewart Wang; Fiscal Year: 2000
    ..We propose to study the factors controlling the production of LBP by cells other than hepatocytes and to compare them to production by hepatocytes themselves...
    Nelson Fausto; Fiscal Year: 2000
    During liver regeneration after partial hepatectomy (PH), normally quiescent hepatocytes enter the cell cycle and replicate...
  74. IKKbeta:Bi-Functional Regulator of Hepatocyte Proliferation
    Hyam L Leffert; Fiscal Year: 2010
    ..Many convergent intracellular pathways have been identified that regulate cyclin D1 expression in hepatocytes, but there are no reports that IKK[unreadable] is among them...