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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 | Sofosbuvir and Ribavirin Prevent Recurrence of HCV Infection after Liver Transplantation: An Open-Label Study显示文摘 | Michael P. Curry Xavier Forns Raymond T. Chung Norah A. Terrault Robert Brown Jonathan M. Fenkel Fredric Gordon Jacqueline O’Leary Alexander Kuo Thomas Schiano Gregory Everson Eugene Schiff Alex Befeler Edward Gane Sammy Saab John G. McHutchison G. Mani S | 2014 | Gastroenterology2014，，： | 3 |
| 3 | 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 |
| 4 | Cd buffering capacity and accumulation in swiss chard in some sludge- amended soils显示文摘 | Kuo S | 1990 | Soil Sci Am J1990，54，： | 2 |
| 5 | Comparative studies on the hypolipidemic and growth suppressive effects of oolong, black, pu-erh, and green tea leaves in rats显示文摘 | Kuo K L Weng M S Chiang C T | 2005 | Journal of Agricultural and Food Chemistry2005，53，2： | 1 |
| 6 | 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 |
| 7 | Video object tracking using adaptive Kalman filter显示文摘 | WENG S K KUO C M TU S K | 2006 | Journal of Visual Communication and Image Representation2006，17，6： | 1 |
| 8 | 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 |
| 9 | A scrambling method for fingerprint positioning based on temporal diversity and spatial dependency 显示文摘 | Kuo S P Tseng Y C | 2008 | IEEE Transactions on Knowledge and Data Engineering2008，20，5： | 1 |
| 10 | A comparison of the pulmonary bioavailability of powder and liquid aerosol formulations of salmon ealcitonin 显示文摘 | Clark A Kuo M C Newman S | 2008 | Pharm Res2008，25，7： | 1 |
| 11 | 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 |
| 12 | Vehicle Body Structure Durability Analysis显示文摘 | Kuo E Y Kelkar S G | 1995 | SAE paper 9501961995，，： | 1 |
| 13 | The process of electrochemical deposited hydroxyapatite coatings on biomedical titanium at room temperature显示文摘 | KUO M C YEN S K | 2002 | Mater Sci Eng2002，20，： | 1 |
| 14 | Topological representations and characteristics of variable kinematic joints显示文摘 | YAN H S KUO C H | 2006 | Transactions of the ASME: Journal of Mechanical Design2006，128，2： | 1 |
| 15 | 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 |
| 16 | 显示文摘 | Xu H Y Kuo S W Huang C F | 2004 | J Appl Polym Sci2004，91，： | 1 |
| 17 | Wettability and superhydrophilic TiO2 film formed by chemical vaopor deposition显示文摘 | Kuo C S Tseng Y H Li Y Y | 2006 | Chemistry Letters2006，，4： | 1 |
| 18 | An assessment of testing-effort dependent software reliability growth models 显示文摘 | HUANG C Y KUO S Y LYU M R | 2007 | IEEE Trans on Reliability2007，56，2： | 1 |
| 19 | Improvability of assembly systems II: improvability indicators and case study 显示文摘 | CHIANG S Y KUO C T LIM J T | 2000 | Mathematical Problems in Engineering2000，6，4： | 1 |
| 20 | Evaluation of fusaric acid as a factor in development of Fusarium wilt显示文摘 | Kuo M S Seheffer R P | 1964 | Phytopathology1964，54，： | 1 |
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