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您的检索式：作者名="Brian Gabrielli"
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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 |
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