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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 | Effect of different probiotic preparations on anti- Helicobacter pylori therapy-related side effects: a parallel group, triple blind, placebo-controlled study显示文摘 | Filippo Cremonini Simona Di Caro Marcello Covino Alessandro Armuzzi Maurizio Gabrielli Luca Santarelli Enrico C Nista Giovanni Cammarota Giovanni Gasbarrini Antonio Gasbarrini | 2002 | The American Journal of Gastroenterology2002，，11： | 2 |
| 3 | A nuclear protein,synthesized in growth-arrested human hepatoblastoma cells,is a novel member of the short-chain alcohol dehydrogenase family显示文摘 | Gabrielli F Donadel G Bensi G | 1995 | Eur J Biochem1995，232，2： | 1 |
| 4 | Histone-deacetylase inhibitors for the treatment of cancer 显示文摘 | Lindemann RK Gabrielli B Johnstone RW | 2004 | Cell Cycle2004，3，6： | 1 |
| 5 | A review of the probabilistic aspects of localized corrosion显示文摘 | GABRIELLI C HUET F KEDDAM M KEDDAM M OLTRA R | 1990 | Corrosion1990，46，4： | 1 |
| 6 | Randomized,double-blind comparison of immediate-release omeprazole oal suspension versus intravenous cimetiding for the prevention of upper gastrointestinal bleeding in critically ill patients显示文摘 | Conrad SA Gabrielli A Margolis B | 2005 | Crit care med2005，33，4： | 1 |
| 7 | Hot Workability and Mod- els for Flow Stress of NIMONIC 115 Ni Base Superalloy 显示文摘 | Bruni C Forcellese A Gabrielli F | 2002 | Journal of Materials Processing Technology2002，125，126： | 1 |
| 8 | Randomized, double - blind comparison of immediate - release omeprazole oral suspension versus intravenous cimetidine for the prevention of upper gastrointestinal bleeding in critically ill patients 显示文摘 | Conrad SA Gabrielli A Margolis B | 2005 | Crit Care Med2005，33，4： | 1 |
| 9 | Alpha-melaocyte stimulating hormone potentiates P16/CDKN2A expression in human skin after ultraviolet irradiation显示文摘 | Pavey S Gabrielli B | 2002 | Cancer Res2002，62，3： | 1 |
| 10 | The role of intestinal microbiota and the immune system显示文摘 | Purchiaroni F Tortora A Gabrielli M | | 0，，03： | 1 |
| 11 | Study of electrochemical phase formation and dissolution by ac quartz electrogravimetry显示文摘 | Boukrane S Gabrielli C Keddam M | 1989 | Electrochim Acta1989，34，8： | 1 |
| 12 | Direct determina- tion of levoglucosan at the picogram per milliliter level in Ant- arctic ice by high-performance liquid chromatography/electros- pray ionization triple quadrupole mass spectrometry显示文摘 | Gambaro A Zangrando R Gabrielli P | 2008 | Analyt- ical Chemistry2008，80，5： | 1 |
| 13 | Blood ariations in internal carotid and middle cerebral arteries indwed by postmenopausal hormone neplace ment therapy显示文摘 | Penotti M Nencioni T Gabrielli L | 1993 | Am J Obstet Gynecol1993，169，5： | 1 |
| 14 | Acquartz crystalmicrobalance applied to the studies of the nickel hydroxide behavior in alkaline solutions显示文摘 | BERNARD P GABRIELLI C KEDDAM M | 1991 | Electrochimica Acta1991，36，34： | 1 |
| 15 | Management of acute lower limb ischemia associated with the Angio-Seal arterial puncture closing device 显示文摘 | Siani A Accrocca F Gabrielli R | 2011 | Interact Cardiovase Thorac Surg2011，12，： | 1 |
| 16 | Genomic organization of the human gene Hep27:alternative promoter usage in HepG2 cells and monocyte-derived dendritic cells显示文摘 | Heinz S Krause S W Gabrielli F | 2002 | Genomics2002，79，4： | 1 |
| 17 | Analysis of electrochemical noise by power spectral density applied to corrosion studies显示文摘 | Bertocci U Frydman J Gabrielli C | 1998 | J Electrochemist Soc1998，145，8： | 1 |
| 18 | Effect of tempera- ture, strain rate and fiorientation on the plastic flow behavior and formability of AZ31 magnesium alloy 显示文摘 | Bruni C Forcellese A Gabrielli F | 2010 | Journal of Ma- terials Pr-essing Technology2010，，210： | 1 |
| 19 | Methadone therapy for opioid dependence显示文摘 | Krambeer LL Mcknelly WV Gabrielli W | 2001 | Am Fam Physician2001，63，12： | 1 |
| 20 | Small intestinal bacterial overgrowth : diagnosis and treatment 显示文摘 | Gasbarrini A Lauritano EC Gabrielli M | 2007 | Dig Dis2007，25，3： | 1 |
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