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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 | A technique for the modal analysis of sound-structure interaction problems显示文摘 | Bokil V B Shirahatti | 1994 | Journal of Sound and Vibration1994，175，1： | 1 |
| 3 | Molecular genetics of long QT syndrome显示文摘 | Nilesh J. Bokil John M. Baisden Dorothy J. Radford Kim M. Summers | 2010 | Molecular Genetics and Metabolism2010，，1： | 1 |
| 4 | Test standards for thermosyphon-type solar domestic hot water system: Review and experimental evaluation 显示文摘 | JOSHI S V BOKIL R S NAYAK J K | 2005 | Sol Energy2005，78，： | 1 |
| 5 | Homogenization of periodically varying coefficients in electromagnetic materials显示文摘 | Bank H T Bokil V A Cioranescu D Gibson N L Griso G Miara B | 2006 | J Sci Comput2006，28，23： | 1 |
| 6 | Comparing spectra and coherences for groups of unequal size 显示文摘 | BOKIL H PURPURA K SCHOFFELEN J M | 2007 | J Neurosci Methods2007，159，2： | 1 |
| 7 | The Brain Arias Concordance Problem:Quantitative Comparison of Anatomical Parcellations显示文摘 | Bohland JW Bokil H Allen C B | 2009 | PLoS One2009，4，9： | 1 |
| 8 | A technique for the modal- analysis of sound structure interaction problems显示文摘 | Bokil VB Shirahatti US | 1994 | Journal of Sounfl and Vibration1994，173，1： | 1 |
| 9 | Molecular genetics of long QT syndrome 显示文摘 | Bokil N J Baisden J M Radford D J | 2010 | Mol Genet Metab2010，101，1： | 1 |
| 10 | Quasi-Three-Dimensional Approach to Simulate the Two-Phase Fluid Flow and Heat Transfer in Condensers 显示文摘 | Zhang C Bokil A A | 1997 | International Journal of Heat and Mass Transfer1997，40，15： | 1 |
| 11 | Test standards for thermosyphon-type solar domestic hot water system: review and experimental evaluation显示文摘 | S.V. Joshi R.S. Bokil J.K. Nayak | 2004 | Solar Energy2004，，6： | 1 |
| 12 | Dynamic phenotypes : Time series analysis techniques {or characterizing neuronal and behavioral dynamics 显示文摘 | Bokil H Tchernichovsky O Mitra P P | 2006 | Neuroinformatics2006，4，1： | 1 |
| 13 | A technique for the modal analysis of sound-structure interaction problems显示文摘 | Bokil V B Shirahatti V S | 1994 | J Sound and Vibration1994，173，1： | 1 |
| 14 | A quasi-three-dimensional approach to simulate the two-phase fluid flow and heat transfer in condensers显示文摘 | ZHANG C BOKIL A | 1997 | International Journal of Heat and Mass Transfer1997，40，15： | 1 |
| 15 | A Quasi-Three-Dimensional Approach to Simulate the Two-Phase Fluid Flow and Heat Transfer in Condensers 显示文摘 | Zhang C Bokil A | 1997 | International Journal of Heat and Mass Transfer1997，40，15： | 1 |
| 16 | A quasi-three-dimension- al approach to simulate the two-phase fluid flow and heat transfer in condensers显示文摘 | ZHANG C BOKIL A | 1997 | International Journal of Heat and Mass Transfer1997，40，10： | 1 |
| 17 | Experimental and bioinformatic eharacterisation of the promoter re- gion of the Marfan syndrome gene, FBN1 显示文摘 | Summers KM Bokil NJ Baisden JM | 2009 | Ge- nomics2009，94，4： | 1 |
| 18 | Chronux: a platform for analyzing neural signals显示文摘 | Bokil H Andrews P | 2010 | Journal of Neuroscience Methods2010，192，1： | 1 |
| 19 | Chronux: A Platform for Analyzing Neural Signals显示文摘 | Hemant Bokil | 2010 | J Neurosci Methods2010，192，1： | 1 |
| 20 | Molecular genetics of long QT syndromes显示文摘 | Bokil N J Baisden JM Radford DJ | 2010 | Mol Genet Metab2010，101，1： | 1 |
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