Gene expression profiling in biliary epithelial cells of primary biliary cirrhosis using laser capture microdissection and cDNA microarray.

ABSTRACT

UNLABELLED Primary biliary cirrhosis (PBC) is a chronic, cholestatic liver disease characterized by progressive destruction of interlobular bile ducts that leads to biliary cirrhosis. To elucidate the etiology of PBC, the gene expression profile in biliary epithelial cells (BECs) was analyzed. Liver specimens of 5 PBC, 3 chronic hepatitis C (CHC), and 3 normal subjects were obtained. BECs were selectively collected by laser capture microdissection (LCM), RNA were obtained by extraction and amplification with T7 RNA polymerase, and a cDNA microarray analysis was performed. The following genes exhibited increased expression in BEC of PBC, as compared with CHC or normal subjects: human leukocyte antigen DQ alpha 1 (HLA-DQA-1), carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1), tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), and vascular cell adhesion molecule 1 (VCAM-1). The immunohistochemistry for HLA-DQA-1, CEACAM1, TRAIL, and VCAM-1 confirmed these results. Furthermore, two-way cluster analysis showed that the gene expression profiling in BEC of PBC were categorized into a separate cluster, distinct from CHC or normal subjects. CONCLUSIONS: The gene expression profiling in BEC of PBC differed from those of CHC and normal subjects, and the genes concerning local immune response, such as HLA-DQA-1, CEACAM1, TRAIL, and VCAM-1, exhibited increased expression, indicating that they were involved in the development of bile duct injury.