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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 | Complications of intracerebral haemorrhage显示文摘 | Joyce S Balami Alastair M Buchan | 2012 | Lancet Neurology2012，，1： | 3 |
| 3 | Change of images of South Korea among foreign tourists after the 2002 FIFA World Cup显示文摘 | Samuel S K Alastair M M | 2005 | Tourism Management2005，26，2： | 1 |
| 4 | An experimental study of viscous flows in contractions 显示文摘 | McNeil D A Addlesee J Alastair S | 1999 | Journal of Loss Prevention in the Process Industries1999，12，： | 1 |
| 5 | Molecular diagnostics for fungal plant pathogens显示文摘 | H Alastair M Foster S J Fraaije B A | 2003 | Pest Man- agement Science2003，59，2： | 1 |
| 6 | Yoga tourism as Niche within the wellness tourism market 显示文摘 | Lehto Xinran Y Brown S Chen Yi & Alastair Morrison | 2006 | Tourism Recreation Research2006，31，1： | 1 |
| 7 | Change of images of south korea among foreign tourists after the 2002 FIFA World Cup 显示文摘 | SAMUEL S K ALASTAIR M M | 2005 | Tourism Management2005，26，： | 1 |
| 8 | Using Desktop GIS for the Investigation of Accessibility by Public Transport显示文摘 | David S Alastair M | 2002 | An Isochrones Approach Geographical Information Science2002，3，1： | 1 |
| 9 | The effects of a highly viscous liquid phase on vertically upward two-phase flow in a pipe 显示文摘 | DAVID A M ALASTAIR D S | 2003 | International Journal of Multiphase Flow2003，29，： | 1 |
| 10 | Periprosthetic hip and knee fractures:The scope of the problem 显示文摘 | | 1998 | Inst Course Lect1998，47，： | 1 |
| 11 | Metamodel-based collaborative optimization framework 显示文摘 | Parviz M Z Vassili V T Alastair S W | 2009 | Structural and Multidisciplinary Optimizatiort2009，38，2： | 1 |
| 12 | An automated flow for arithmetic component Generation in Field-Programmable Gate Arrays显示文摘 | Alastair M S George A C Peter Y K | 2008 | ACM Transactions on Reconfigurable Technology and Systems2008，，： | 1 |
| 13 | A tale of two Web spaces : comparing sites using Web impact factors 显示文摘 | Alastair G S | 1999 | Journal of Documentation1999，，5： | 1 |
| 14 | Using desktop GIS for the investigation of accessibility by public transport:An isochrone approach显示文摘 | DAVID S ALASTAIR M SHEARER J | 2000 | International Journal of Geographical Information Science2000，14，1： | 1 |
| 15 | An experimental study of viscous flows in contractions显示文摘 | MCNEIL DAVID A ADDLESEE J ALASTAIR S | 1999 | Journal of Loss Prevention in the Process Industries1999，12，4： | 1 |
| 16 | Neurological complications of acute ischaemic stroke显示文摘 | Joyce S Balami Ruo-Li Chen Iris Q Grunwald Alastair M Buchan | 2011 | Lancet Neurology2011，，： | 1 |
| 17 | Protein and lipid composition of bovine mmilk-fatglobule membrane 显示文摘 | BERTRAM Y F CARMEN S N ALASTAIR K H | 2006 | International Dairy Journal2006，17，： | 1 |
| 18 | Combined Oral Positive Inotropic and Beta-Blocker Therapy for Treatment of Refractory Class IV Heart Failure显示文摘 | Simon F Shakar William T Abraham Edward M Gilbert Alastair D Robertson Brian D Lowes Lawrence S Zisman Debra A Ferguson Michael R Bristow | 1998 | Journal of the American College of Cardiology1998，，： | 1 |
| 19 | Guidelines on the diagnosis and management of multiple myeloma 显示文摘 | Alastair S Finn W Diana S | 2005 | Br 1 Haematol2005，132，6： | 1 |
| 20 | Selective small molecule inhibitors of glycogen synthase kinase-3 modulate glycogen metabolism and gene transcription显示文摘 | Matthew P Coghlan Ainsley A Culbert Darren AE Cross Stacey L Corcoran John W Yates Nigel J Pearce Oliver L Rausch Gregory J Murphy Paul S Carter Lynne Roxbee Cox David Mills Murray J Brown David Haigh Robert W Ward David G Smith Kenneth J Murray Alastair | 2000 | Chemistry & Biology2000，，10： | 1 |
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