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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 | 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 |
| 3 | 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 |
| 4 | Two-and three-liq- uid phase equilibria in the system water + 2-heptanone + caprolac- tam + ammonium sulfate : Experiments and modeling 显示文摘 | van Bochove G H Krooshof G J P de Loos T W | 2002 | Fluid Phase Equilibria2002，194，： | 1 |
| 5 | Relationship between phenolic acids formed during rumen degradation of maize samples and in vitro digestibility显示文摘 | Marvin H J P Krechting C F Van Loo E N | 1996 | Journal of the Science of Food and Agriculture1996，71，： | 1 |
| 6 | TCFTL2 polymorphisms modulate proinsulin levels and Cell function in a British Europid population 显示文摘 | LOOS R J FRANKS P W FRANCIS R W | 2007 | Diabetes2007，56，7： | 1 |
| 7 | Light gap disturbance,recruitment limitation,and tree diversity in a neotropical forest显示文摘 | Hubbell S P Foster R B O'Brian S T Harms K E Condit R Wechsler B Wright S J Loo de Lao S | | 0，，： | 1 |
| 8 | Wear resistance of PVD-coating in roller bearings显示文摘 | Gold P W Loos J | 2002 | Wear2002，25，3： | 1 |
| 9 | Degradation of poly(lactide-co-glycolide) (PLGA) and poly(L-lactide)(PLLA) by electron beam radiation显示文摘 | J S C Loo C P Ooi F Y C Boey | | 0，，： | 1 |
| 10 | Flow and compaction during the vacuum assisted resin transfer moulding process显示文摘 | Grimsley B W Pascal H Song X L Cano R J Loos A C Byron P R | 2001 | International SAMPE Technology Conference2001，33，： | 1 |
| 11 | Preparation of conductive nanotube-polymer composites using latex technology显示文摘 | Regev O E1Kati P N B Loos J and Koning C E | 2004 | Advanced Materials2004，16，3： | 1 |
| 12 | Doping γ-Fe2O3 nanoparticles with Mn (Ⅲ) suppresses the transition to the α- Fe2O3 structure 显示文摘 | Lai J Shafi K V P M Loos K | 2003 | J Am Chem Soc2003，125，11： | 1 |
| 13 | relationships and heritability estimates of traits in lobolly pine(P/nus taede) 显示文摘 | LOO J A TANER C G Van BUIJTEN J P | 1984 | Can J For Res1984，14，： | 1 |
| 14 | Immune reconstitution of CD56(dim) NK cells in individuals with primary HIV-I infection treated with interleukin-2 显示文摘 | Michaelsson J Long B R Loo C P | 2008 | J Infect Dis2008，197，1： | 1 |
| 15 | Thermal conductivity of thin SiO2 films显示文摘 | LOOS P J BRADY D P | 1992 | Thin Solid Films1992，207，： | 1 |
| 16 | The inlluence of the processing conditions on the performance of electrically con- ductive carbon nanotube/polymer nanocomposites 显示文摘 | Grossiord N Kivit P J J Loos J | 2008 | Polym2008，49，12： | 1 |
| 17 | Effect of isothermal annealing on the hydrolytic degradation rate of poly(lactide-co-glycolide) (PLGA) 显示文摘 | Loo S C J Ooi C P Wee S H E | 2005 | Biomaterials2005，26，： | 1 |
| 18 | The prevalence and types of glaucoma in malay people : the Singapore Malay Eye Study 显示文摘 | Shen SY Wong TY Foster P J Loo JL Rosman M Loon SC | 2008 | Invest Ophthalmol Vis Sci2008，49，9： | 1 |
| 19 | 显示文摘 | Loo J S C Ooi C P Boey F Y C | 2005 | Biomaterials2005，26，12： | 1 |
| 20 | Relationship between phenolic acids formed during rumen degradation of maize samples and in vitro digestibility显示文摘 | Marvin H J P Krechting C F Van Loo E N | 1996 | Journal of the Science of Food and Agriculture1996，71，： | 1 |
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