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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 | Cubic AgPb, SbTez+,, : bulk thermoelectric materials with high figure of merit 显示文摘 | Hsu K F Loo S Guo F Chen W Dyck J S Uher C Hogan T Polychroniadis E K Kanatzidis M G | 2004 | Science2004，303，： | 1 |
| 3 | Costimulatory molecules in human atherosclerotic plaques: an indication of antigen specific T lymphocyte activation显示文摘 | Onno J de Boer Floris Hirsch Allard C van der Wal Chris M van der Loos Pranab K Das Anton E Becker | 1997 | Atherosclerosis1997，，2： | 1 |
| 4 | Induction of B7-1in podocytes is associated with nephritic syndrome显示文摘 | Reiser J yon Gersdorff G Loos M | 2004 | J Clin Invest2004，113，10： | 1 |
| 5 | Activation of ribu- lose - 1, 5 - bisphosphate carboxyiase/oxygenase (Rubisco) involves Rubisco activase Trpl6 显示文摘 | VAN DE LOO F J SALVUCCI M E | 1996 | Bio- chemistry1996，35，25： | 1 |
| 6 | Con- sumers' willingness to pay for organic chicken breast: evi- dence from choice experiment显示文摘 | VAN LOO E J CAPUTO V NAYGA J R M | 2011 | Food Quality and Prefer- ence2011，22，7： | 1 |
| 7 | Dietary modulation of the human colonic microbiota:updating the concept of prebiotics显示文摘 | GIBSON G R PROBERT H M VAN LOO J | 2004 | Nutrition Research Reviews2004，17，2： | 1 |
| 8 | Consumer attitudes, knowledge, and consumption of organic yogurt显示文摘 | VAN LOO E J DIEM M N H PIENIAK Z | 2013 | Journal of Dairy Science2013，96，4： | 1 |
| 9 | Studies on Prn variation in the mouse model and comparison with epidemlologi- cal data 显示文摘 | Van Gent M Van Loo IH Heuvelman K J | 2011 | PLoS One2011，6，18： | 1 |
| 10 | Surgery of malignant pancreatic tumors 显示文摘 | Loos M Friess H Kleeff J | 2009 | Radiologe2009，49，2： | 1 |
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| 12 | Dietary modulation of the human colonic microbiota: updating the concept of prebiotics 显示文摘 | Gibson G R Probert H M Loo J V | 2004 | Nutrition Research Reviews2004，17，2： | 1 |
| 13 | Induction of B7-1 in podocytes is associated with nephrotic syndrome显示文摘 | REISER J von GERSDORFF G LOOS M | 2004 | J Clin Invest2004，113，10： | 1 |
| 14 | Consumers' Willing- ness to Pay for Organic Chicken Breast: Evidence from Choice Experiment 显示文摘 | Van Loo E J Caputo V Nayga R M | 2011 | Food Quality and Preference2011，22，7： | 1 |
| 15 | The bifidogenic nature of chicory inulin and its hydrolysis products显示文摘 | ROBERFROID M B van LOO J A E GIBSON G R | 1998 | J Nutr1998，128，1： | 1 |
| 16 | Prediction of fatigue crack initiation for rolling contact fatigue显示文摘 | Ringsberg J W Loo Morrey M Josefson B L | 2000 | International Journal of Fatigue2000，22，3： | 1 |
| 17 | Design and application of self-assembled low molecular weight hydrogels显示文摘 | Loos M Feriuga B L Esch J H | 2005 | Eur J Org Chem2005，，17： | 1 |
| 18 | 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 |
| 19 | Common variants near MC4R are associated with fat mass, weight and risk of obesity 显示文摘 | Loos R J F Lindgren C M Li S | 2008 | Nature Genetics2008，40，6： | 1 |
| 20 | Adventitial infiltrates associated with advanced atherosclerotic plaques: structural organization suggests generation of local humoral immune responses 显示文摘 | Houtkamp M A de Boer O J van der Loos C M | 2001 | J Pathol2001，193，2： | 1 |
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