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World J Gastroenterol. Sep 28, 2014; 20(36): 13088-13104
Published online Sep 28, 2014. doi: 10.3748/wjg.v20.i36.13088
Published online Sep 28, 2014. doi: 10.3748/wjg.v20.i36.13088
Osteopontin is an important mediator of alcoholic liver disease via hepatic stellate cell activation
Devanshi Seth, Paul S Haber, Drug Health Services, Royal Prince Alfred Hospital, Camperdown, NSW 2050, Australia
Alastair Duly, Garvan Institute, Darlinghurst, NSW 2010, Australia
Devanshi Seth, Paul S Haber, Central Clinical School of Medicine, the University of Sydney, Sydney, NSW 2050, Australia
Paul C Kuo, Department of Surgery, Loyola University Medical Centre, Maywood, IL 60153, United States
Geoffrey W McCaughan, AW Morrow Gastroenterology and Liver Centre, RPAH, Camperdown, NSW 2050, Australia
Author contributions: Seth D wrote and revised the manuscript, designed, performed and supervised human, cell culture; Animal experiments performed by Duly A; Kuo PC supplied reagents and expert advice for OPN aptamer experiments; McCaughan GW provided critical review of the manuscript; Haber PS assisted with human sample collection, clinical expertise and critical review of the manuscript.
Supported by Philanthropic Anonymous Source; the University of Sydney Bridging Support Grant, in part for Honours Project; and by the National Health and Medical Research Council, No. NHMRC Practitioner Research Fellowship for PH support
Correspondence to: Devanshi Seth, Principal Scientist, Drug Health Services, Royal Prince Alfred Hospital, Missenden Road, Camperdown, NSW 2050, Australia. d.seth@sydney.edu.au
Telephone: +61-2-95157201 Fax: +61-2-95158970
Received: January 3, 2014
Revised: March 11, 2014
Accepted: April 30, 2014
Published online: September 28, 2014
Processing time: 271 Days and 7.5 Hours
Revised: March 11, 2014
Accepted: April 30, 2014
Published online: September 28, 2014
Processing time: 271 Days and 7.5 Hours
Core Tip
Core tip: The present study confirms a novel hypothesis that alcohol induced plasmin is mediated via Osteopontin (OPN) in hepatic stellate cell (HSC). We show that OPN has a key role in alcohol-induced HSC functions such as signalling, cell migration and activation of fibrinolysis, extracellular matrix and fibrogenic pathways. Identification of transcriptional isoform OPN-C in patients with alcoholic cirrhosis and LX2, and proteolytically cleaved cOPN in mice with a single dose of alcohol is novel. Importantly, we have defined novel mechanisms of OPN action in alcohol-induced liver injury that have a broader significance in other forms of liver injury.