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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 | Bit-wise paral lel algorithms for efficient software correlation applied to a GPS soft ware receiver显示文摘 | LEDVINA B M PSIAKI M L POWELL S P | 2004 | IEEE Transactions on Wireless Communications2004，3，5： | 1 |
| 3 | Reduced drag coefficient for high wind speeds in tropical cyclones显示文摘 | POWELL M D VICKERY P J REINHOLD T A | 2003 | Nature2003，422，： | 1 |
| 4 | Wind-driven surface transport in stratified closed basins: Direct versus residual circulations显示文摘 | Strub P T Powell T M | 1986 | Journal of Geophysical Research1986，91，7： | 1 |
| 5 | Hydraulic conductivity of a recent estuarine silty clay at Bothkennar显示文摘 | LEROUEIL S LERAT P HIGHT D W POWELL J J M | 1992 | Geotechnique1992，42，2： | 1 |
| 6 | Reduced drag coefficient for high wind speeds in tropical cyclones 显示文摘 | POWELL M D VICKERY P J REINHOLD T A | 2005 | Nature2005，422，6929： | 1 |
| 7 | Information systems strategy for small and medium sized enterprises:An organization perspective显示文摘 | LEVY M POWELL P | 2000 | Strategic Information systems2000，，9： | 1 |
| 8 | Barriers to supply chain information integration:SMEs adrift of eLands显示文摘 | Harland C M Caldwell N D Powell P | 2007 | Journal of Operations Management2007，25，6： | 1 |
| 9 | Effects of backwash conditions on out-to-in membrane microfiltration显示文摘 | HILLIS P PADLEY M B POWELL N I | 1998 | Desalination1998，118，13： | 1 |
| 10 | Reduced drag coefficient for high wind speeds in tropical cyclones 显示文摘 | Powell M D Vickery P J Reinhold T A | 2003 | Nature2003，422，： | 1 |
| 11 | Microflow - based automated chemistries : ap- plication to protein sequencing 显示文摘 | M Powell P Tempst | 2001 | Analytical Chemistry2001，73，4： | 1 |
| 12 | An expansin gene expressed in ripening strawberry fruit显示文摘 | Civello P M Powell A LT Sabehat A | 1999 | Plant Physiology1999，121，： | 1 |
| 13 | Regulation of metal absorption in the gastrointestinaltract 显示文摘 | Whitehead M W Thompson R P H Powell J J | 1996 | Gut1996，39，： | 1 |
| 14 | Phase II study of sorafenib incombination with docetaxel and cisplatin in the treatment of meta-static or advanced gastric and gastroesophageal junction adenocarci-noma: ECOG 5203 显示文摘 | Sun W Powell M O'Dwyer P J | 2010 | J Clin Oncol2010，28，18： | 1 |
| 15 | Creep and microstructure of magnesium-aluminum-calcium based alloys 显示文摘 | LUO A A BALOGH M P POWELL B R | 2002 | Metallurgical and Materials Transactions2002，33，： | 1 |
| 16 | Nitrogen use ef- ficiency: A potential performance indicator and policy tool for dairy farms 显示文摘 | Powell J M Gourley C J P Rotz C A | 2010 | Environmental science policy2010，13，3： | 1 |
| 17 | Effects of early childhood psychosocial stimulation and nutritional supplementation on cognition and education in growth-stunted Jamaican children: prospective cohort study显示文摘 | Susan P Walker Susan M Chang Christine A Powell Sally M Grantham-McGregor | 2005 | The Lancet2005，，9499： | 1 |
| 18 | Early results of external iliac artery stenting combined with com- mon femoral artery endarterectomy 显示文摘 | Nelson P R Powell R J Schermerhorn M L | 2002 | J Vasc Surg2002，35，6： | 1 |
| 19 | The convergence of variable metric matrices in the unconstrained optimization显示文摘 | Ge R P Powell M J D | 1983 | Methmatical Programming1983，27，： | 1 |
| 20 | Plate tectonics and the Himalayas显示文摘 | Powell C M Conaghan P J | 1973 | Earth and Planetary Science Letters1973，20，： | 1 |
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