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Toxicologic Pathology, Vol. 34, No. 4, 373-384 (2006)
DOI: 10.1080/01926230600806543

Articles

The Temporal Expression of Osteopontin (SPP-1) in the Rodent Model of Alcoholic Steatohepatitis: A Potential Biomarker

Atrayee Banerjee1, Robert C. Burghardt2, Greg A. Johnson2, Frankie J. White2 and Shashi K. Ramaiah1

1 Department of Pathobiology and
2 Veterinary Integrative Biosciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX 77843-4467, USA

Correspondence: Address correspondence to: Shashi K. Ramaiah, Department of Pathobiology, College of Veterinary Medicine, Texas A&M University, College Station, TX 77843-4467; e-mail:sramaiah{at}cvm.tamu.edu

Previous studies from our laboratory have shown that osteopontin (OPN) mediates neutrophil infiltration into the liver in a rodent model of alcoholic steatohepatitis (ASH). The objective of this study was to investigate the temporal and spatial pattern of hepatic OPN mRNA and protein expression during the progression of alcoholic liver disease. OPN mRNA and protein expression were evaluated using real time PCR, in situ hybridization, Western blot and immunohistochemistry respectively. ASH was induced in male Sprague–Dawley rats by feeding EtOH-containing Lieber-DeCarli diet for 6 weeks, followed by a single injection of lipopolysaccharide (LPS, 10 mg/kg, ip). Rats were sacrificed 2-, 12- and 24-hour post LPS injection. A progressive induction of OPN mRNA was observed that preceded hepatic neutrophil infiltration and the increase in OPN mRNA correlated with increases in OPN protein expression. OPN mRNA was localized primarily to the biliary epithelium. The data indicates that OPN is transcribed and translated within the biliary epithelium. These findings suggest a potential role of OPN as an early biomarker in predicting inflammatory liver diseases such as ASH.

Key Words: Alcoholic steatohepatitis • biomarkers • diagnostic pathology • hepatic • inflammation • osteopontin


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