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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 | On the production of hydrogen sulfide - sulfur mixtures from deep formations显示文摘 | Kuo C H | 1972 | Sept1972，1142，： | 2 |
| 3 | Simulation of deployment dynamics of inflatable structures 显示文摘 | SALAMA M KUO C P MICHAEL L | 2000 | AIAA Journal2000，38，12： | 2 |
| 4 | Hydrophobic interactions in complexes of antimicrobial peptides with bacterial polysaccharides 显示文摘 | KUO H H CHAN C BURROWS L L | 2007 | Chem Biol Drug Des2007，69，6： | 1 |
| 5 | Urodynamic results of intravesical heparin therapy for women with frequency urgency syndrome and interstitial cystitis显示文摘 | Kuo H C | 2001 | J Formos Med Assoc2001，100，5： | 1 |
| 6 | Fever,consciousness disturbance,and muscle rigidity in a 68-year-old man with depressive disorder 显示文摘 | Tsai H C Kuo P H Yang P C | 2003 | Chest2003，124，4： | 1 |
| 7 | 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 |
| 8 | 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 |
| 9 | 显示文摘 | Smith R | 1998 | Transactions of International Chemical Engineering(Part A)1998，76，： | 1 |
| 10 | 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 |
| 11 | Development of the High Concentration Ⅲ-Ⅴ Photovoltaic System at INER, Taiwan 显示文摘 | Kuo C T Shin H Y Hong H F | 2009 | Renewable Energy2009，34，8： | 1 |
| 12 | Environmentally conscious design and manufacturing:a state of-the-art survey 显示文摘 | Hong C Zhang Tsai C Kuo Huitian Lu | 1997 | Journal of Manufacturing Systems1997，16，5： | 1 |
| 13 | 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 |
| 14 | 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 |
| 15 | 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 |
| 16 | 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 |
| 17 | Fuzzy neural networks with application to sales for casting显示文摘 | Kuo R J Xue K C | 1999 | Fuzzy Sets and Systems1999，108，： | 1 |
| 18 | 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 |
| 19 | Highly efficient expression of fish growth hormone by Escherichia coli cells显示文摘 | Tsai H J Lin K L Kuo J C | 1995 | Applied and Environmental Microbiology1995，61，11： | 1 |
| 20 | Dielectric properties of three ceramic/epoxy composites显示文摘 | Kuo D H Chang C C Su T Y | 2004 | Mater Chem Phys2004，85，1： | 1 |
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