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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 | Development of Precipitation Hardening Cr-Mo-Co Stainless Steel显示文摘 | Kasak A Chandhok C k Dulis E J | 1963 | Trans ASM1963，56，： | 1 |
| 3 | Influence of potassium deficiency on photosynthesis,chlorophyll contentand chloroplast ultra structure of cotton plants显示文摘 | ZHAO Duli D M OOSTERHUIS C W BEDNARZ | | 0，，01： | 1 |
| 4 | Quarantine Strawberry vein banding virus firstly detected in Slovakia and Serbia显示文摘 | Petrzik K Mráz I Duli(c)-Markovi(c) I | | 0，，02： | 1 |
| 5 | Effect of Interstitial Carbon Plus Nitrogen and Precipitation Reactions on the Properties of Austenitic Cr-Mn-C-N Steels显示文摘 | Hsaio C M Dulis E J | | 0，，： | 1 |
| 6 | Development of precipitation hardening Cr-Mo-Go stainless steels显示文摘 | Kasak A Chandhok C K Dulis E J | 1963 | Trans ASM1963，56，： | 1 |
| 7 | Recombinant human erythropoietin for chronic renal failure anaemia in pre-dialysis patients显示文摘 | CODY J DULY C CAMPBELL M | 2005 | Coehrane Dtabase Syst Rev2005，，3： | 1 |
| 8 | Use of ribozyme and antisense oligodeoxynucleotides to investigate mechanism of drug resistance 显示文摘 | Byrne D Duly C Nicamhlaoibh R | 1998 | Cytotechnology1998，27，13： | 1 |
| 9 | Development of precipita- tion hardening 2Mo2Co stainless steel显示文摘 | KasakA Chandhok C K Dulis E J | 1963 | Trans ASM1963，56，： | 1 |
| 10 | Development of Precipitation Hardening Cr-Mo-Co Stainless Steels显示文摘 | Kasak A Chandhok C K Dulis E J | 1963 | Trans ASM1963，56，： | 1 |
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