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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 | Clinical determination of myocardial vs load effects of OPC-18790,a novel intravenous agent for the treatment of patients with congestive heart failure显示文摘 | Feldman M D Haber H L Wu C C | 1993 | Circulation1993，88，42： | 1 |
| 3 | An investigation of tool-wear monitoring in a high-speed machining process显示文摘 | Haber R E Jimenez J E Peres C R | 2004 | Sensors and Actuators A:Physical2004，116，3： | 1 |
| 4 | Toward Intelligent Machining: Hierarchical Fuzzy Control for the End Milling Process 显示文摘 | HABER R E PERES C R ALIQUE A | 1998 | IEEE Transactions on Control Systems Technology1998，6，2： | 1 |
| 5 | Sufentanil pharma-cokinetics in patients with cirrhosis显示文摘 | Chauvin M Rerri ER C Haberer JP | 1989 | Anaesth Analg1989，68，1： | 1 |
| 6 | Type-A Arabidopsis re-sponse regulators are partially redundant negative regulators of cytokininsignaling显示文摘 | TO J P C HABERER G FERREIRA F J | 2004 | Plant Cell2004，16，： | 1 |
| 7 | The major genetic determinants of HIV-1control affect HLA class I peptide presentation显示文摘 | International HIV Controllers Study Pereyra F Jia X McLaren P J Telenti A de Bakker P I Walker B D Ripke S Brumme C J Pulit S L Carrington M Kadie C M Carlson J M Heckerman D Graham R R Plenge R M Deeks S G Gianniny L Crawford G Sullivan J Gonzalez E Davies L Camargo A Moore JM Beattie N Gupta S Crenshaw A Burtt N P Guiducci C Gupta N Gao X Qi Y Yuki Y Piechocka-Trocha A Cutrell E Rosenberg R Moss K L Lemay P O'Leary J Schaefer T Verma P Toth I Block B Baker B Rothchild A Lian J Proudfoot J Alvino D M Vine S Addo M M Allen T M Altfeld M Henn M R Le Gall S Streeck H Haas D W Kuritzkes D R Robbins G K Shafer R W Gulick R M Shikuma C M Haubrich R Riddler S Sax P E Daar E S Ribaudo H J Agan B Agarwal S Ahern R L Allen B L Altidor S Altschuler E L Ambardar S Anastos K Anderson B Anderson V Andrady U Antoniskis D Bangsberg D Barbaro D Barrie W Bartczak J Barton S Basden P Basgoz N Bazner S Bellos N C Benson A M Berger J Bernard N F Bernard A M Birch C Bodner S J Bolan R K Boudreaux E T Bradley M Braun J F Brndjar J E Brown S J Brown K Brown S T Burack J Bush LM Cafaro V Campbell O Campbell J Carlson R H Carmichael J K Casey K K Cavacuiti C Celestin G Chambers S T Chez N Chirch L M Cimoch P J Cohen D Cohn LE Conway B Cooper D A Cornelson B Cox D T Cristofano M V Cuchural G Jr Czartoski J L Dahman J M Daly J S Davis B T Davis K Davod S M DeJesus E Dietz C A Dunham E Dunn M E Ellerin T B Eron J J Fangman J J Farel C E Ferlazzo H Fidler S Fleenor-Ford A Frankel R Freedberg K A French N K Fuchs JD Fuller J D Gaberman J Gallant J E Gandhi R T Garcia E Garmon D Gathe J C Jr Gaultier C R Gebre W Gilman F D Gilson I Goepfert P A Gottlieb M S Goulston C Groger R K Gurley T D Haber S Hardwicke R Hardy W D Harrigan P R Hawkins T N Heath S Hecht F M Henry W K Hladek M Hoffman R P Horton J M Hsu R K Huhn G D Hunt P Hupert M J Illeman M L Jaeger H Jellinger R M John M Johnson J A Johnson K L Johnson H Johnson K Joly J Jordan W C Kauffman C A Khanlou H Killian R K Kim A Y Kim D D Kinder C A Kirchner J T Kogelman L Kojic E M Korthuis P T Kurisu W Kwon D S LaMar M Lampiris H Lanzafame M Lederman M M Lee D M Lee J M Lee M J Lee E T Lemoine J Levy J A Llibre J M Liguori M A Little S J Liu A Y Lopez A J Loutfy M R Loy D Mohammed D Y Man A Mansour M K Marconi V C Markowitz M Marques R Martin J N Martin H L Jr Mayer K H McElrath M J McGhee T A McGovern B H McGowan K McIntyre D Mcleod GX Menezes P Mesa G Metroka CE Meyer-Olson D Miller A O Montgomery K Mounzer K C Nagami E H Nagin I Nahass R G Nelson M O Nielsen C Norene D L O'Connor D H Ojikutu B O Okulicz J Oladehin O O Oldfield E C Olender S A Ostrowski M Owen WF Jr Pae E Parsonnet J Pavlatos A M Perlmutter A M Pierce M N Pincus J M Pisani L Price L J Proia L Prokesch R C Pujet H C Ramgopal M Rathod A Rausch M Ravishankar J Rhame F S Richards C S Richman D D Rodes B Rodriguez M Rose R C 3rd Rosenberg E S Rosenthal D Ross P E Rubin D S Rumbaugh E Saenz L Salvaggio M R Sanchez WC Sanjana V M Santiago S Schmidt W Schuitemaker H Sestak P M Shalit P Shay W Shirvani V N Silebi V I Sizemore J M Jr Skolnik P R Sokol-Anderson M Sosman J M Stabile P Stapleton J T Starrett S Stein F Stellbrink H J Sterman FL Stone V E Stone D R Tambussi G Taplitz R A Tedaldi E M Telenti A Theisen W Torres R Tosiello L Tremblay C Tribble M A Trinh P D Tsao A Ueda P Vaccaro A Valadas E Vanig T J Vecino I Vega V M Veikley W Wade B H Walworth C Wanidworanun C Ward D J Warner D A Weber R D Webster D Weis S Wheeler D A White D J Wilkins E Winston A Wlodaver C G van't Wout A Wright D P Yang O O Yurdin D L Zabukovic B W Zachary K C Zeeman B Zhao M | 2010 | Science2010，330，6010： | 1 |
| 8 | QT prolongation and recurrent torsade de pointes during erythromycin lactobionate infusion 显示文摘 | Bedock B Chartier C Haberer JP | 1986 | Am J Cardiol1986，58，： | 1 |
| 9 | Sulfur metabolism in plants:Are trees different?显示文摘 | Rennenberg H Herschbach C Haberer K | 2007 | Plant Biology2007，9，： | 1 |
| 10 | Relationship between left ventricular wall thickness and left atrial size: Comparison with other measures of diastolic function显示文摘 | Feldman M D Haber H L | 1995 | J Am Soc Echocardiogr1995，8，1： | 1 |
| 11 | In vivo MRI-based 3D FSI RV/ LV models for human right ventricle and patch design for potential computer-aided surgery optimization显示文摘 | Yang C Tang D Haber I | 2007 | Compdters & Structures2007，85，11： | 1 |
| 12 | A new approach to variable-topology shape using a constraint on perimeter 显示文摘 | Haber R B Jog C S Bendsoe M P | 1996 | Structural Optimization1996，11，1： | 1 |
| 13 | A bayesian network model for biomarker-based dose response 显示文摘 | Hack C Eric Haber Lyrme T Maier Andrew | 2010 | Blackwell Publishing Inc2010，30，7： | 1 |
| 14 | Morphologically selec-tive synthesis of nanocrystalline aluminum nitride显示文摘 | Haber J A Gibbons P C Bubro W E | 1998 | Chemis-try of Materials1998，，10： | 1 |
| 15 | Topology design with opti-mized, self-adaptive materials显示文摘 | JOG C S HABER R B | 1994 | International Journal for Numerical Methods in Engineering1994，37，： | 1 |
| 16 | Studies on the reduction and re- formation of protein disulfide bonds显示文摘 | ANFINSEN C B HABER E | 1961 | Journal of Biological Chemistry1961，236，5： | 1 |
| 17 | The benefit ofstrength training on arterial blood pressure in patients with type 2 diabetes mellitus measured with ambulatory 24-hour blood pressure systems显示文摘 | Strasser B Haber P Strehblow C | 2008 | Wiener Medizinische Wochen- schrifl2008，158，1314： | 1 |
| 18 | Nature and course of pancreatitis caused by 6-mercaptopurine in the treatment of inflammatory bowel disease 显示文摘 | Haber C J Meltzer S J Present DH | 1986 | Gastroenterology1986，91，： | 1 |
| 19 | Type-A Arabidop- sis response regulators are partially redundant negative regulators of cytokinin signaling显示文摘 | To J P C Haberer G Ferreira F J | 2004 | Plant Cell2004，16，： | 1 |
| 20 | Stability of finite elements models for distributed-parameter optimization and topology design 显示文摘 | JOG C S HABER R B | 1996 | Computer Methods in Applied Meehanies and Engineering1996，130，34： | 1 |
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