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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 | On the Dynamic Response of a Suspended Cable显示文摘 | H M Irvine J H Griffin | 1974 | Earthquake Engineering and Structural Dynamics1974，4，： | 2 |
| 3 | Standardized measurement of the future liver remnant prior to extended liver resection: Methodology and clinical associations显示文摘 | Jean-Nicolas Vauthey Amin Chaoui Kim-Anh Do Malcolm M Bilimoria Marc J Fenstermacher Chuslip Charnsangavej Marshall Hicks Guido Alsfasser Gregory Lauwers Irvin F Hawkins James Caridi | 2000 | Surgery2000，，5： | 2 |
| 4 | Developmental analysis of elongation factor-1 expression in transgenic tobacco显示文摘 | URSIN V M IRVINE J M HIATT W R SHEWMAKER C K | 1991 | Plant Cell1991，3，6： | 1 |
| 5 | Suppression of avian influenza transmission in genetically modified chickens 显示文摘 | LYALL J IRVINE R M SHERMAN A | 2011 | Science2011，331，6014： | 1 |
| 6 | Pokeweed antiviral protein inactivates pokeweed ribosomes implications for the antiviral mechanism显示文摘 | BONNESS M S READY M P IRVIN J D | 1994 | Plant J1994，5，2： | 1 |
| 7 | Regional citrate anticoagulation in continuous venovenous hemodiafiltration显示文摘 | Irvin M Wu Dat NC | 2000 | Am J Kidney Dis2000，35，5： | 1 |
| 8 | lmmunolgical aspects of premure ovarian failure associated with idiopathic Addison' s disease显示文摘 | Chan M W Scarth L | 1968 | Lancet1968，2，： | 1 |
| 9 | Fire hazards and some common polymers 显示文摘 | IRVINE D J MCCLUSKEY J A ROBINSON I M | 2000 | Polym Degrad Stab2000，67，3： | 1 |
| 10 | Inositol trisphosphate, a novel second messenger in cellular signal transductiou 显示文摘 | Berridge M J Irvine RF | 1984 | Nature1984，312，5992： | 1 |
| 11 | Gephsical exploration for epithermal gold deposits显示文摘 | Irvine R J Smith M J | 1990 | Journal of Geochemical Exploration1990，，36： | 1 |
| 12 | Monitoring the sensible heat flux over urban areas using large aperture scintillometry: Case study of Marseille city during the escompte experiment显示文摘 | Lagouarde J P M Irvine J M Bonnefond | 2006 | Boundary Layer Meteor2006，118，3： | 1 |
| 13 | Fire hazards and some common polymers 显示文摘 | Irvine D J McCluskey J A Robinson I M | 2000 | Polymer Degradation and Stability2000，67，： | 1 |
| 14 | Polymer latexes for cell-resistant and cell-interactive surfaces显示文摘 | BANERJEE P IRVINE D J MAYES A M | 2000 | Biomed Mater Res2000，50，3： | 1 |
| 15 | Pokeweed Antiviral Protein: Ribosome Inactivation and Therapeutic Applications显示文摘 | Irvin J D Uckun F M | 1992 | Pharmacol Ther1992，55，： | 1 |
| 16 | Seismic damage in reinforced concrete frames 显示文摘 | Banon H Biggs J M Irvine H M | 1981 | Journal of Structural Engineering ASCE1981，107，9： | 1 |
| 17 | Suppression of avian influenza transmission in genetically modified chickens显示文摘 | Lyall J Irvine R M Sherman A | 2011 | Science2011，331，6014： | 1 |
| 18 | On the dynamic response of a suspended cable显示文摘 | Irvine H M Griffin J H | 1974 | Earthquake Engineering and Structural Dynamics1974，4，： | 1 |
| 19 | T cell killing does not require the formation of a stable mature immunological synapse 显示文摘 | Purbhoo M A Irvine D J Huppa J B | 2004 | Nature Immunology2004，5，： | 1 |
| 20 | Influence of structure and composition upon performance of tin phosphate based negative electrodes for lithium batteries显示文摘 | Behm M Irvine J T S | 2002 | Electrochimica Acta2002，47，11： | 1 |
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