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| 1 | Osteopontin is an important mediator of alcoholic liver disease via hepatic stellate cell activation显示文摘AIM: To investigate over-expression of Osteopontin(OPN) pathway expression and mechanisms of action in human alcoholic liver disease(ALD), in vivo and in vitro acute alcohol models. METHODS: OPN pathway was evaluated in livers from patients with progressive stages of human ALD and serum from drinkers with and without liver cirrhosis. In vitro stellate LX2 cells exposed to acute alcohol and in vivo in acute alcoholic steatosis mouse models were also investigated for OPN pathway expression and function. WT and OPN-/- mice were administered an acute dose of alcohol and extent of liver injury was examined by histopathology and liver biochemistry after 16-24 h. The causative role of OPN was studied in OPN knockout animals and in vitro in stellate LX2 cells, utilizing siRNA, aptamer and neutralizing antibodies to block OPN and OPN pathway. OPN pathway expression and downstream functional consequences were measured for signaling by Western blotting, plasmin activation by spectrophotometric assays and cell migration by confocal imaging and quantitation. RESULTS: OPN expression positively correlated with disease severity in patients with progressive stages of ALD. In vivo, associated with alcoholic steatosis, a single dose of acute alcohol significantly increased hepatic OPN mRNA and protein, and a cleaved OPN form in a dose dependent manner. OPN mRNA and secreted OPN also increased in parallel with activation of LX2 stellate cells within 4 h of a single dose of alcohol. Expression of OPN receptors, αvβ3-integrin and CD44, increased in human ALD, and in vivo and in vitro with alcohol administration. This was accompanied by downstream phosphorylation of Akt and Erk, increased mRNA expression of several fibrogenesis, fibrinolysis and extracellular matrix pathway genes, plasmin activation and hepatic stellate cell(HSC) migration. Inhibition of OPN and OPN-receptor mediated signaling partially inhibited alcohol-induced HSC activation, plasmin activity and cell migration. CONCLUSION: OPN is a key mediator of the alcoholinduced effects on hepatic stellate cell functions and liver fibrogenesis. | Devanshi Seth Alastair Duly Paul C Kuo Geoffrey W McCaughan Paul S Haber | 2014 | World Journal of Gastroenterology2014，20，36： | 5 |
| 2 | The analysis of piezoelectric/piezomagnetic composites materials containing ellipsoidal inclusions 显示文摘 | HUANG J H KUO W S | 1997 | J Appl Phys1997，81，3： | 2 |
| 3 | Synthesis and macroscopic secondorder nonlinear optical properties of poly (ether imide)s containing a novel two-dimensional carbazole chromophore with nitro acceptors显示文摘 | Kuo W J Hsiue G H Jeng R J | 2002 | J Mater Chem2002，12，： | 2 |
| 4 | Comparison of RBCA and CalTOX for Setting Risk-Based Cleanup Levels Based on Inhalation Exposure 显示文摘 | CHANG S H KUO C Y WANG J W | 2004 | Chemosphere2004，56，4： | 1 |
| 5 | 显示文摘 | Smith R | 1998 | Transactions of International Chemical Engineering(Part A)1998，76，： | 1 |
| 6 | Poly(oxyalkylene)diamine-functionalized carbon nanotube/perfluorosulfonated polymer composites:Synthesis,water state,and conductivity显示文摘 | CHEN W F WU J S KUO P L | 2008 | Chem Mater2008，20，6： | 1 |
| 7 | Effects of insulin replacement on cardiac apoptotic and survival pathways in streptozotocin-induced diabetic rats显示文摘 | Kuo W W Chung L C Liu C T | 2009 | Cell Biochem Funct2009，27，7： | 1 |
| 8 | The analysis of piezoelectric/piezo- magnetic composites materials containing ellipsoidal inclu- sions显示文摘 | Huang J H Kuo W S | 1997 | J Appl Phys1997，81，： | 1 |
| 9 | Evaluation of the ability of an artificial neural net work model to assess the variation of groundwater quality in an area of black foot disease in Taiwan 显示文摘 | Kuo Y M Liu C W Lin K H | 2004 | Water Research2004，38，1： | 1 |
| 10 | High color rendering white light-emitting-diode illuminator using the red-emitting Eu^2+ -activated CaZnOS phosphors excited by blue LED 显示文摘 | Kuo T W Liu W R Chen T M | 2010 | Optics Express2010，18，8： | 1 |
| 11 | Real-time garbage collection for flash-memory storage systems of realtime embedded systems 显示文摘 | Chang L P Kuo T W Lo S W | 2004 | ACM Transactions on Embedded Computing Systems2004，3，4： | 1 |
| 12 | 显示文摘 | Xu H Y Kuo S W Huang C F | 2004 | J Appl Polym Sci2004，91，： | 1 |
| 13 | Simulation study of surface-plasmon-resonance electro-optic light modulatorbased on a polymer grating coupler 显示文摘 | Kuo W K Chen M T | 2009 | Opt Lett2009，34，24： | 1 |
| 14 | The Chinese Version of the Facts on Aging Quiz Scale: Reliability and Validity Assessment显示文摘 | Wang C C Liao W C Kuo P C | 2010 | Int J Nurs Stud2010，47，6： | 1 |
| 15 | An application of particle swarm optimization algorithm to clustering analy- sis显示文摘 | KUO R J WANG M J HUANG T W | 2011 | Soft Computing2011，15，3： | 1 |
| 16 | A fast MPEG-7 dominant color extraction with new similarity measure for image retrieval 显示文摘 | Yang N C Chang W H Kuo C M | 2008 | Journal of Visual Communication and Image Representation2008，19，2： | 1 |
| 17 | Facile synthesis of composite electrodes containing platinum particles distributed in nanowires of polyaniline-poly(acrylic acid) for methanol oxidation显示文摘 | Kuo C W Yang C C Wu T | 2011 | International Journal of Electrochemical Science2011，6，： | 1 |
| 18 | Quantifying energy use, carbon dioxide emission, and other environmental loadsfrom island tourism based on a life cycle assessment approach显示文摘 | Kuo N W Chen P H | 2009 | Journal of Cleaner Production2009，17，15： | 1 |
| 19 | Some recent advances on importance measures in reliability显示文摘 | Kuo W Zhu X | 2012 | IEEE Transactions on Reliability2012，61，2： | 1 |
| 20 | Comparative study of optimization techniques for irrigation project planning显示文摘 | KUO S F LIU C W CHEN S K | 2013 | Journal of the American Water Resources Association2013，39，1： | 1 |
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