Bioinformatic approach for cholangiocyte pathophysiology

The heterogeneous functions of cholangiocytes regulate the physiology of the biliary epithelium regarding secretory, proliferative and apoptotic activities. However, due to their technical difficulties for isolation and culture, the pathophysiology of cholangiocytes was poorly understood. Recently, cutting-edge technology, such as the microarray, has given the opportunity for investigating cholangiocytes. We have found the distinct expression profiles of two murine cholangiocytes lines, termed small and large, revealed by microarray analysis. The features of the two cholangiocyte cell lines, categorized partly according to gene ontology, indicate the specific physiological role of each cell line. Namely, large cholangiocytes are characterized as "transport" and "immune/inflammatory responses". In contrast to large, small cholangiocytes are associated with properties of limited physiological functional ability and proliferating/ migratingpotential with specific molecules like Eph receptors, comparable to mesenchymal cells. Further analysis using other modern technology, such as proteomics, will provide more information to understand the pathophysiology of cholangiocytes. These novel methods enable us to investigate the key molecules and their mutual relationship. Although the evaluation of some important biological regulatory processes like protein modification requires methodologies other than microarray, microarray technology is anticipated to grow with the development of data-analysis theory for the comprehension of cellular cross-talk in the liver.