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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 | Damage mechanics approach for bearing lifetime prognostics显示文摘 | Qiu J Zhang C Seth B B Liang S Y | 2002 | Mechanical Systems and Signal Processing2002，16，5： | 1 |
| 3 | The effect of grammage of sheet properties显示文摘 | Seth R S Hanturen J T Moss C S | 1989 | Appita Journal1989，42，1： | 1 |
| 4 | Selectivity sequences andsorption capacities of phosphatic clay and humus rich soil towards theheavy metals present in zinc mine tailing显示文摘 | CHATURVEDI P K SETH C S MISRA V | 2007 | Journal of Hazardous Mate-rials2007，147，3： | 1 |
| 5 | Phytoextraction of toxic metals:a central role for glutathione 显示文摘 | Seth C S Remans T Keunen E | 2012 | Plant cell & environment2012，35，2： | 1 |
| 6 | The effect of grammage on sheet properties显示文摘 | Seth R S Jantunen J T Moss C S | 1989 | Appita1989，42，1： | 1 |
| 7 | Appfieation of the SHE to catehment in India-Part 1:C,eneralresuits显示文摘 | SETH S M BATHURST J C | 1992 | J of Hydrol1992，140，： | 1 |
| 8 | Plant regeneration from cotyledons of Prunus persica,Prunus domestica,and Prunus cerasus显示文摘 | SETH M RALPH S JOHN M C | 1989 | Plant Cell Tissue and Organ Culture1989，19，： | 1 |
| 9 | Antihista- minic and spasmolytic effects of musk 显示文摘 | Seth S D Mukhopadhyay A B Prbhakar M C | 1973 | Jpn J Pharmacol1973，23，5： | 1 |
| 10 | Crystal structure of the orthorhombic U2-Al4Mg4Si4 precipitate in the Al-Mg-Si alloy system and its relation to theand phases显示文摘 | ANDERSEN S J MARIOARA C D Frseth A | 2005 | Materials Science and Engineering2005，390，： | 1 |
| 11 | Application of the SHE to catchments in India: part I: general results 显示文摘 | REFSGAARD J C SETH S M BATHURST J C | 1992 | Journal of Hydrology1992，140，： | 1 |
| 12 | Anti- arrhythmie effects of prostaglandins E2 and I2 on ouaba- in-induced cardiac arrhythmias in cats : effect of vagoto-my and adrenergic neuron blockade 显示文摘 | RAO T S SETH S D MANCHANDA S C | 1990 | Pharmacologi- cal Research1990，22，2： | 1 |
| 13 | A facile electrochemical app :oach for development of highly corrosion protective coatings using graphene nanosheets 显示文摘 | SAHU S C SAMANTARA A K SETH M | 2013 | Electrochemistry Communications2013，32，： | 1 |
| 14 | Effects of adenovirus-mediated p16INK4A expression on cell cycle arrest are determined by endogenous p16 and Rb status in human cancer cells显示文摘 | Craig C Kim M Ohri E Wersto R Katayose D Li Z Choi YH Mudahar B Sfivastava S Seth P Cowan K | 1998 | Oncogene1998，16，： | 1 |
| 15 | Oil extraction rates of soyabean using isopropyl alcohol as solvent显示文摘 | SETH S AGRAWAL Y C GHOSH P K | 2007 | Biosystems Engineering2007，97，2： | 1 |
| 16 | Effect of moisture content onthe quality of soybean oil and meal extracted by isopropyl alcohol and hex-ane显示文摘 | SETH S AGRAWAL Y C GHOSH P K | 2010 | Food and Bioprocess Technology2010，3，1： | 1 |
| 17 | Damage mechanics approach for bearing lifetime prognostics显示文摘 | Qiu J Zhang C Seth B Liang S Y | 2002 | Mechanical Systems and Signal Processing2002，16，5： | 1 |
| 18 | Genotoxicity of cadmium on root meristem cells of Alliurn cepa:eytogenetic and Comet assay approach显示文摘 | SETH C S MISRA V CHAUHAN L K | 2008 | Ecotoxicology and Environmental Safety2008，71，3： | 1 |
| 19 | Periodic heat transfer through a hollow concreter slab: Optimum placement of the air gap显示文摘 | Sodha M S Seth A K Kaushik S C | 1980 | Applied Energy1980，6，2： | 1 |
| 20 | The effect of grammage of sheet properties显示文摘 | Seth R S Hanturen J T Moss C S | 1989 | Appita Journal1989，42，1： | 1 |
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