Clusterin expression in cholestasis, hepatocellular carcinoma and liver fibrosis.
OBJECTIVE
Clusterin shares functional properties with small heat shock proteins. In contrast to other heat shock proteins, it is present in the extracellular space. Its expression is altered in various diseases. The aim was to evaluate the presence and distribution of clusterin in liver diseases associated with cholestasis, in fibrosis and in hepatocellular carcinoma.


RESULTS
Tissue microarrays and biopsy materials were used to evaluate immunohistochemically the expression of clusterin in hepatocellular carcinoma, primary sclerosing cholangitis, primary biliary cirrhosis, mechanical cholestasis, drug-induced cholestasis, liver fibrosis and cirrhosis. The presence of clusterin in human bile was assessed by Western blotting. Furthermore, real-time reverse transcriptase-polymerase chain reaction was performed on liver tissue with mechanical cholestasis. Clusterin colocalized with elastic fibres, but not with collagen, hepatocytes or bile duct epithelia. It was detected in bile plugs in cholestasis and hepatocellular carcinomas with pseudoglandular features within the lumina. Clusterin was demonstrated in bile by Western blotting and its mRNA was expressed in normal and cholestatic livers.


CONCLUSIONS
Clusterin may protect bile duct epithelium against offensive biliary components or inhibit precipitation of biliary proteins. The association of clusterin with elastic fibres could reflect an extracellular chaperone function by either protecting elastic fibres or shielding abnormal elastic material.
Institute of Pathology, Medical University of Graz, Graz, Austria.
Ariane
A
Aigelsreiter
Elke
E
Janig
Julia
J
Sostaric
Martin
M
Pichler
Daniela
D
Unterthor
Judith
J
Halasz
Carolin
C
Lackner
Kurt
K
Zatloukal
Helmut
H
Denk
D001646:Bile / Q000737:chemistry / Q000378:metabolism; D001652:Bile Ducts / Q000378:metabolism; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002779:Cholestasis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051152:Clusterin / Q000096:biosynthesis*; D004547:Elastic Tissue / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D008103:Liver Cirrhosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D046888:Tissue Array Analysis
D051152:Clusterin