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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 | Evaluation of a speetrophotometric assay for the measurement of malondialdehyde and 4-hydroxyalkenals in human spermatozoa: relationships with semen quality and sperm function 显示文摘 | Gomez E Irvine D S Aitken R J | 1998 | Int J Androl1998，21，2： | 1 |
| 3 | Evidence of deteriorating semen quality in the United Kingdom:birth cohort study in 577 men in Scotland over 11 years显示文摘 | Irvine S Cawood E Richardson D | 1996 | BMJ1996，312，7029： | 1 |
| 4 | DNA integrity in human spermatozoa : relationships with semen quality 显示文摘 | Irvine D S Twigg J P Gordon E L | 2000 | J Androl2000，21，1： | 1 |
| 5 | Rectal Corticosteroids Versus Aternativet Reatments in Ulcerative Colitis显示文摘 | Marshall J Irvine E | 2000 | Gastioentero2000，95，： | 1 |
| 6 | CCN3-a key regulator of the hematopoietic compartment 显示文摘 | McCallum L Irvine A E | 2009 | Blood Rev2009，23，2： | 1 |
| 7 | The development of genetic transgenic transformation of sugarcane in Texas 显示文摘 | IRVINE J E MIRKOV T E | 1997 | Sugar Journal1997，60，： | 1 |
| 8 | 显示文摘 | Valenzuela R Irvine J T S | 1990 | J Appl Phys1990，，67： | 1 |
| 9 | Posttranscriptional Gene Silencing in Transgenic Sugarcane显示文摘 | Ivan L Ingelbrecht James E Irvine T Erik Mirkov | 1999 | Plant Physiol1999，119，4： | 1 |
| 10 | The frequency of marker changes in sugarcane plants regenerated from callus cuhure显示文摘 | IRVINE J E BENDA G T A LEGENDRE B L | 1991 | Plant Cell Tissue and Organ Culture1991，26，2： | 1 |
| 11 | Contrasting soil respiration in young and old-growth ponderosa pine forests 显示文摘 | Irvine J Law B E | 2002 | Global Change Biology2002，8，12： | 1 |
| 12 | Health-related quality of life in functional GI disorders focus on constipation and resource utilizatian显示文摘 | IRVINE E J FERRAZZI S PARE P | 2002 | Am Gastroenterol2002，97，7： | 1 |
| 13 | Effect of a phytoestrogen food supplement on reproductive health in normal males显示文摘 | Mitchell JH Cawood E Kinniburgh D Provan A Collins AR Irvine DS | 2001 | Clin Sci2001，100，： | 1 |
| 14 | Perinatal mortality and neonatal morbidity rates among twin pairs at different gestational ages: optimal delivery timing at 37 to 38 weeks' gestation显示文摘 | Rebecca SH Irvin E Jane H | 2001 | Am J Obstet Gynecol2001，184，3： | 1 |
| 15 | Evaluations ofvisible implant fluorescent tags for marking coho salmon smolts显示文摘 | BAILEY R E IRVINE J R DALZIEL F C | 1998 | North American Journal of Fisheries Management1998，18，： | 1 |
| 16 | Protcasome inhibitors in cancer therapy显示文摘 | Crawford L J Walker B Irvine A E | 2011 | J Cell Commun Signal2011，5，2： | 1 |
| 17 | Quality of life measurement in gastrointestinal and liver disorders 显示文摘 | Borgaonkar M R Irvine E J | 2000 | Gut2000，47，3： | 1 |
| 18 | Peptide tyrosine arginine,a potent immunomodulatory peptide isolated and structurally characterized from the skin secretions of the dusky gopher frog,Rana sevosa显示文摘 | Graham C Irvine A E Mcclean S | 2005 | Peptides2005，26，5： | 1 |
| 19 | Functional gastrointestinal disorders in Canada:first population-based survey using Rome Ⅱ criteria with suggestions for improving the questionnaire显示文摘 | Thompson W G Irvine E J Pare O | 2002 | Dig Dis Sci2002，47，： | 1 |
| 20 | The Formaldehyde Ortho/para Ratio As a Probe of Dark Cloud Chemistry and Evolution 显示文摘 | DICKENS J E IRVINE W M | 1999 | J Astrophys1999，518，： | 1 |
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