Disease- and Cell-Specific Expression of GP73 in Human Liver Disease

GP73, a Golgi membrane protein, is expressed at high levels in hepatocytes of patients with decompensated cirrhosis. Its expression in other forms of liver disease has not been investigated. Therefore, we studied GP73 expression in patients with noncirrhotic liver disease. GP73 expression was detect...

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Published in:	The American journal of gastroenterology Vol. 99; no. 6; pp. 1087 - 1095
Main Authors:	IFTIKHAR, Rehan, KLADNEY, Raleigh D, HAVLIOGLU, Necat, SCHMITT-GRÄFF, Annette, GUSMIROVIC, Ilijas, SOLOMON, Harvey, LUXON, Bruce A, BACON, Bruce R, FIMMEL, Claus J
Format:	Journal Article
Language:	English
Published:	Oxford Blackwell Publishing 01-06-2004 Wolters Kluwer Health Medical Research, Lippincott Williams & Wilkins
Subjects:	Acute Disease Analysis of Variance Biological and medical sciences Blotting, Western Case-Control Studies Cells, Cultured Chronic Disease Female Gastroenterology Gastroenterology. Liver. Pancreas. Abdomen Gene Expression Regulation Genetic Markers Hepatitis, Autoimmune - genetics Hepatitis, Autoimmune - pathology Hepatitis, Viral, Human - genetics Hepatitis, Viral, Human - pathology Hepatocytes Humans Immunohistochemistry Liver Cirrhosis - genetics Liver Cirrhosis - pathology Male Medical sciences Membrane Proteins - genetics Microscopy Microscopy, Confocal Probability Prognosis Sampling Studies Sensitivity and Specificity Human Digestive diseases Hepatic disease Disease Cell Gastroenterology
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Summary:	GP73, a Golgi membrane protein, is expressed at high levels in hepatocytes of patients with decompensated cirrhosis. Its expression in other forms of liver disease has not been investigated. Therefore, we studied GP73 expression in patients with noncirrhotic liver disease. GP73 expression was detected immunohistochemically and by immunofluorescence microscopy in patients with acute hepatitis of various etiologies, autoimmune hepatitis, chronic HCV infection, and alcoholic liver disease. In order to quantitate hepatocyte GP73 expression, an immunohistochemical scoring system was developed, and validated by a direct comparison with GP73 protein levels as determined by Western blotting. GP73 immunostaining and Western blotting data were highly correlated, demonstrating the suitability of the immunohistochemical scoring system to quantitate hepatocyte GP73 expression. Hepatocyte GP73 expression was increased in patients with acute and autoimmune hepatitis. Treatment of autoimmune hepatitis was associated with a normalization of GP73 expression, indicating that the initial upregulation was reversible. Increased levels of GP73 expression were also noted in chronic HCV infection and alcoholic liver disease. Under these conditions, GP73 levels were correlated with disease stage but not grade. GP73 immunoreactivity was occasionally detected in alpha-SMA-positive, sinusoidal lining cells, suggesting activated stellate cells as a potential source of GP73. Hepatocyte GP73 levels are upregulated in acute hepatitis and during the progression of liver disease to cirrhosis. This expression pattern suggests the presence of two regulatory mechanisms, the first triggered during acute hepatocellular injury, the second during the progression of chronic liver disease.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0002-9270 1572-0241
DOI:	10.1111/j.1572-0241.2004.30572.x