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| 1 | Senescent human hepatocytes express a unique secretory phenotype and promote macrophage migration显示文摘AIM:To develop a model of stress-induced senescence to study the hepatocyte senescence associated secretory phenotype(SASP).METHODS:Hydrogen peroxide treatment was used to induce senescence in the human Hep G2 hepatocyte cell line.Senescence was confirmed by cytochemical staining for a panel of markers including Ki67,p21,heterochromatin protein 1β,and senescence-associated-β-galactosidase activity.Senescent hepatocytes were characterised by gene expression arrays and quantitative polymerase chain reaction(q PCR),and conditioned media was used in proteomic analyses,a human chemokine protein array,and cell migration assays to characterise the composition and function of the hepatocyte SASP.RESULTS:Senescent hepatocytes induced classical markers of senescence(p21,heterochromatin protein1β,and senescence-associated-β-galactosidase activity);and downregulated the proliferation marker,Ki67.Hepatocyte senescence induced a 4.6-fold increase in total secreted protein(P=0.06)without major alterations in the protein profile.Senescence-induced genes were identified by microarray(Benjamini Hochbergcorrected P<0.05);and,consistent with the increase in secreted protein,gene ontology analysis revealed a significant enrichment of secreted proteins among inducible genes.The hepatocyte SASP included characteristic factors such as interleukin(IL)-8 and IL-6,as well as novel components such as SAA4,IL-32and Fibrinogen,which were validated by q PCR and/or chemokine protein array.Senescent hepatocyteconditioned medium elicited migration of inflammatory(granulocyte-macrophage colony stimulating factor,GM-CSF-derived),but not non-inflammatory(CSF-1-derived)human macrophages(P=0.022),which could contribute to a pro-inflammatory microenvironment in vivo,or facilitate the clearance of senescent cells.CONCLUSION:Our novel model of hepatocyte senescence provides insights into mechanisms by which senescent hepatocytes may promote chronic liver disease pathogenesis. | Katharine M Irvine Richard Skoien Nilesh J Bokil Michelle Melino Gethin P Thomas Dorothy Loo Brian Gabrielli Michelle M Hill Matthew J Sweet Andrew D Clouston Elizabeth E Powell | 2014 | World Journal of Gastroenterology2014，20，47： | 2 |
| 2 | Ataxin-2 associates with the endocytosis complex and affects EGF receptor trafficking显示文摘 | Nonis D Schmidt MH van de Loo S | 2008 | Cell Signal2008，20，10： | 1 |
| 3 | Streptococcus gordonii biofilm formation: identification of genes that code for biofilm phenotypes显示文摘 | LOO C Y CORLISS D A GANESHKUMAR N | 2000 | Journal of Bacteriology2000，182，5： | 1 |
| 4 | The polycomb group protein Bmi-1 is essential for the growth of multiple myeloma cells显示文摘 | Jagani Z Wiederschain D Loo A | | 0，，13： | 1 |
| 5 | A study of the thermal denaturation of ribonuclease S by electrospray ion ization mass spectrometry 显示文摘 | GOODLETT D R LOO R R O LOO J A | 1994 | J Am Soc Mass Spectrom1994，5，7： | 1 |
| 6 | Technology spillovers between sectors and over time显示文摘 | VERSPAGEN B LOO I D | 1999 | Technological Forecasting and social change1999，，60： | 1 |
| 7 | Effect of Iron Ore Par- ticle Assimilation on Sinter Structure 显示文摘 | Debrincat D Loo C E Hutchens M F | 2004 | ISIJ Int2004，44，8： | 1 |
| 8 | Active sugar transport in health and disease 显示文摘 | WRIGHT E M HIRAYAMA B A LOO D F | 2007 | J Intern Med2007，261，1： | 1 |
| 9 | Clinical Pharmaeokinetics of unbound docetaxel: Role of Polysorbate 80 and Serum Proteins显示文摘 | Waiter J Loos Sharyn D Baker Jaap Verweij MD | 2003 | Clinical Pharmacology & Therapeutics2003，74，： | 1 |
| 10 | Treatment of periodontitis improves the atherosclerotic profile: a systematic review and meta‐analysis显示文摘 | Wijnand J. Teeuw Dagmar E. Slot Hendri Susanto Victor E. A. Gerdes Frank Abbas Francesco D’Aiuto John J. P. Kastelein Bruno G. Loos | 2014 | J Clin Periodontol2014，，1： | 1 |
| 11 | Determination of the dose of ag- omelatine,a melatoninergic agonist and selective 5-HT2C antago- nist,in the treatment of major depressive disorder: a placebo con- trolled dose range study 显示文摘 | Loo H Hale A D'Haenen H | 2002 | In Clin Psychopharmcol2002，17，5： | 1 |
| 12 | Influence of methane on the phase behavior of oil + water + nonionic surfactant 显示文摘 | Rudolph E S J Bovendeert M J Loos T W D | 1998 | Systems Phys Chem1998，102，： | 1 |
| 13 | B7 -h3 and its role in antitumor immunity显示文摘 | LOOS M HEDDERICH D M FRIESS H | 2010 | Clin Dev hnmunol2010，2010，68： | 1 |
| 14 | Collisional effects on the charge distribution of ions from large molecules, formed by electrospray-ionization mass spectrometry显示文摘 | LOO J A UDSETH H R SMITH R D | 1988 | Rapid Commun in Mass Spectrom1988，2，10： | 1 |
| 15 | A double-blind, sham-con- trolled trial of transeranial direct current stimulation for the treatment of depression显示文摘 | Loo CK Sachdev P Martin D et ai | 2010 | Int J Neuropsychopharmacol2010，13，1： | 1 |
| 16 | Viral and therapeutic control of IFN beta promoter stimulator 1 during hepatitis C virus infection显示文摘 | Loo Y M D M Owen K Li et ai | 2006 | Proc Natl Aead Sci USA2006，103，： | 1 |
| 17 | The Industry Employability Index: Taking Account of Supply and Demand Characteristics显示文摘 | Grip A D Loo J V Sanders S J | 2004 | International Labour Review2004，143，3： | 1 |
| 18 | A study by voltammetry and the photocurrent response method of copper electrode behavior in acidic and alkaline solutions containing chloride ions显示文摘 | Modestov A D Zhou G D Ge H H Loo B H | 1995 | Journal of Electroanalytical Chemistry1995，380，3： | 1 |
| 19 | Elevated levels of vascular endothelial growth factor in serum of patients with D+HUS显示文摘 | Maroeska Te Loo D Bosma N Van Hinsbergh V | 2004 | Pediatr Nephrol2004，19，7： | 1 |
| 20 | Tariquidar inhibits P-glycoprotein drug efflux but activates ATPase activity by blocking transition to an open conformation 显示文摘 | LOO T W CLARKE D M | 2014 | Biochem Pharmacol2014，92，4： | 1 |
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