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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 | Implementation of sentinel node biopsy in breast cancer patients in the Netherlands显示文摘 | Ho VK der Loo M Rutgers EJ | 2008 | Eur J Cancer2008,44,5: | 1 |
| 3 | Bcl-2 family members as sentinels of cellular integrity and role of mitochondrial intermembrane space proteins in apoptotic cell death显示文摘 | Festjens N van Gurp M van Loo G Saelens X Vandenabeele P | 2004 | Acta Haematol2004,111,2: | 1 |
| 4 | Cubic AgPb, SbTez+,, : bulk thermoelectric materials with high figure of merit 显示文摘 | Hsu K F Loo S Guo F Chen W Dyck J S Uher C Hogan T Polychroniadis E K Kanatzidis M G | 2004 | Science2004,303,: | 1 |
| 5 | Costimulatory molecules in human atherosclerotic plaques: an indication of antigen specific T lymphocyte activation显示文摘 | Onno J de Boer Floris Hirsch Allard C van der Wal Chris M van der Loos Pranab K Das Anton E Becker | 1997 | Atherosclerosis1997,,2: | 1 |
| 6 | Relevant anatomy for botulinum toxin fa- cial rejuvenation显示文摘 | LOOS B M MAAS C S | 2003 | Facial Plastic Surgery Clinics of North Ameri- ca2003,11,4: | 1 |
| 7 | A novel approach for unit commitment problem via an effective hybrid particle swarm optimization 显示文摘 | TING T O RAO M V C LOO C K | 2006 | IEEE Trans on Power Systems2006,21,1: | 1 |
| 8 | Induction of B7-1in podocytes is associated with nephritic syndrome显示文摘 | Reiser J yon Gersdorff G Loos M | 2004 | J Clin Invest2004,113,10: | 1 |
| 9 | Invariant Object Tracking Using Fringe-adjusted Joint Transform Correlator显示文摘 | Chye-Hwa Loo Alam M S | 2004 | Optical Engineering2004,43,9: | 1 |
| 10 | Activation of ribu- lose - 1, 5 - bisphosphate carboxyiase/oxygenase (Rubisco) involves Rubisco activase Trpl6 显示文摘 | VAN DE LOO F J SALVUCCI M E | 1996 | Bio- chemistry1996,35,25: | 1 |
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| 14 | Dietary modulation of the human colonic microbiota:updating the concept of prebiotics显示文摘 | GIBSON G R PROBERT H M VAN LOO J | 2004 | Nutrition Research Reviews2004,17,2: | 1 |
| 15 | Biophysical characteristics of the pig kidney Na +/glucose cotransporter SGLT2 reveal a common mechanism for SGLT1 and SGLT2 显示文摘 | Mackenzie B Loo DD Panayotova-Heiermann M | 1996 | J Biol chem1996,271,32: | 1 |
| 16 | Tipping the balance between necrosis and apoptosis in human and murine cells treated with interferon and dsRNA显示文摘 | Kalai M Van Loo G Berghe TV | 2002 | Cell Death Differ2002,9,9: | 1 |
| 17 | Interleukin-17 acts independently of TNF-alpha under arthritic conditions显示文摘 | Koenders M I Lubberts E van de Loo F A | 2006 | J Immunol2006,176,10: | 1 |
| 18 | Effects of epigallocatechin gallate and quercetin on oxidative damage to cellular DNA显示文摘 | Johnson M K Loo G | 2000 | Mutation Research2000,459,3: | 1 |
| 19 | State-of-the-art of Co2 capture with ionic liquids显示文摘 | RAMDIN M LOOS T WD VLUGTL TJ H | 2012 | Indus-trial & Engineering Chemistry Research2012,51,24: | 1 |
| 20 | NHE-1 :a promising target for novel anti-cancer therapeutics 显示文摘 | LOO S Y CHANG M K CHUA C S | 2012 | Curr Pharm Des2012,18,10: | 1 |