Disease- and cell-specific expression of GP73 in human liver disease.
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Iftikhar
Rehan
R
Department of Internal Medicine, Division of Gastroenterology and Hepatology, Saint Louis University School of Medicine, St. Louis, Missouri, USA.
Kladney
Raleigh D
RD
Havlioglu
Necat
N
Schmitt-Gräff
Annette
A
Gusmirovic
Ilijas
I
Solomon
Harvey
H
Luxon
Bruce A
BA
Bacon
Bruce R
BR
Fimmel
Claus J
CJ
D000208:Acute Disease; D000704:Analysis of Variance; D015153:Blotting, Western; D016022:Case-Control Studies; D002478:Cells, Cultured; D002908:Chronic Disease; D005260:Female; D005786:Gene Expression Regulation; D005819:Genetic Markers; D019693:Hepatitis, Autoimmune / Q000235:genetics* / Q000473:pathology; D006525:Hepatitis, Viral, Human / Q000235:genetics* / Q000473:pathology; D022781:Hepatocytes; D006801:Humans; D007150:Immunohistochemistry; D008103:Liver Cirrhosis / Q000235:genetics* / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008853:Microscopy; D018613:Microscopy, Confocal; D011336:Probability; D011379:Prognosis; D012494:Sampling Studies; D012680:Sensitivity and Specificity
C410824:GOLM1 protein, human; D005819:Genetic Markers; D008565:Membrane Proteins