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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 | Passengers' airport choice within multiairport regions (MARs): some insights from a stated preference survey at Hong Kong International Airport显示文摘 | Becky P Loo H | 2008 | Journal of Transport Geography2008，，16： | 1 |
| 3 | Bcl-2 family members as sentinels of cellular integrity and role of mitochondrial intermembrane space proteins in apoptotic cell death显示文摘 | Festjens N van Gurp M van Loo G Saelens X Vandenabeele P | 2004 | Acta Haematol2004，111，2： | 1 |
| 4 | Multi-objective simulation-based evolutionary algorithm for an aircraft spare parts allocation problem显示文摘 | Loo H L Ek P C Suyan T | 2008 | European Journal of Operational Research2008，189，： | 1 |
| 5 | High(15 Hz)and low(1 Hz) frequency transcranial magnetic stimulation have different acute ef- fects on regional cerebral blood flow in depressed patients显示文摘 | Loo C K Sachdev P S Haindl W | 2003 | Psy chol Med2003，33，99： | 1 |
| 6 | Gas-phase coordination properties of Zn^2+ Cu^2+ Ni^2+ and Co^2+ with histidine-eontaining peptides显示文摘 | Hu P Loo J A | 1995 | J Am Chem Soc1995，117，11： | 1 |
| 7 | A novel HSP90 modulator with selective activity against thyroid cancers in vitro显示文摘 | Sainadi A Loo P Mukelji R | 2009 | Surgely2009，146，： | 1 |
| 8 | Practical approach to the prediction of rutting in asphalt pavements:the SHELL method显示文摘 | van de LOO P J | 1976 | Journal of the Transportation Research Board1976，616，： | 1 |
| 9 | Multi-objective simulation-based evolutionary algorithm for an aircraft spare parts allocation problem 显示文摘 | Loo H L Ek P C Suyan T | | European Journal of Operational Research0，200，189： | 1 |
| 10 | Expression and glycosylation studies of human FGF receptor 4 显示文摘 | Tuominen H Heikinheimo P Loo BM | 2001 | Protein Expr Pufif2001，21，2： | 1 |
| 11 | Morphology of immature bovine oocytes显示文摘 | De Loos F Van Vliet C van Maurik P V | 1989 | Gamete research1989，24，2： | 1 |
| 12 | Decisions to donate bone Marow: the role of attitudes and subjective norms across cultures显示文摘 | BAGOZZI R P LEE K H LOO M F V | 2001 | Psychology & Health2001，16，1： | 1 |
| 13 | A novel HSP90 modulator with selective activity against thyroid cancers in vitro显示文摘 | Samadi A Loo P Mukerji R | 2009 | Surgery2009，146，6： | 1 |
| 14 | The Impact of Plain Waterjet Machining on the Surface Integrity of Aluminium 7475显示文摘 | Boud F Loo L F Kinnell P K | 2014 | Procedia CIRP2014，13，： | 1 |
| 15 | Double-blind controlled investigation of transeranial magnetic stimulation for the treatment of resistant major depression 显示文摘 | Loo C Mitchell P Saehdev P | 1999 | Am J Psychiatry1999，156，6： | 1 |
| 16 | Trends in cervical squamous cell carcinoma incidence in 13 European countries:changing risk and the effects of screening显示文摘 | Bray F Loos AH Mc Carron P | 2005 | Cancer Epidemiol Biomarkers Prev2005，14，3： | 1 |
| 17 | Carbon dioxide emissions from passenger transport in China since 1949:Implications for developing sustainable transport显示文摘 | LOO B P Y LI L N | 2012 | Energy Policy2012，50，： | 1 |
| 18 | Polysomy 17 in breast cancer :clinicopathologic significance and impact on HER-2 testing 显示文摘 | Vanden Bempt I Van Loo P Drijkoningen M | 2008 | J Clin Oncol2008，26，30： | 1 |
| 19 | Carbon dioxide emissions from passenger transport in China since 1949:Implications for developing sustainable transport显示文摘 | Loo B P Y Li L | 2012 | Energy Policy2012，，11： | 1 |
| 20 | Role of yeast proliferation in the quality degradation of strawberries during refrigerate storage显示文摘 | Ragaert P Devlieghere F Loos S | 2006 | International Journal of Food Microbiology2006，108，： | 1 |
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