Transcriptional profiles of biliary epithelial cells from rat regenerating liver after partial hepatectomy

Abstract

It has been widely accepted that hepatocytes are critical for liver regeneration (LR), but very little is known about the role of biliary epithelial cells (BECs) in this event, so this study aims to manifest the relevance of BECs with LR. High purity population of BECs was obtained using Percoll gradient centrifugation combined with immunomagnetic-bead separation technique. Transcriptional profiles of BECs from rat regenerating liver after 2/3 hepatectomy were monitored with rat genome 230 2.0 array. Microarray analysis results were evaluated by RT-PCR assays. Of all the genes on the array, 1262 known genes and 1026 unknown genes were related to LR. 79 of 1262 known genes showed a ≥ 20-fold change in expression level, mainly participating in primary metabolism and inflammatory response. In contrast to the regenerating liver, BEC division did not occur at proliferative phase of LR; alterations in nucleic acid, lipid and protein metabolism were significantly different from each other or within the same substance metabolism at different phases; the active signaling pathways in priming phase were mediated mainly by G protein-coupled receptor, small GTPase and Wnt receptor. Transport-related genes showed up-regulated expression mainly in priming and proliferative phases, possibly linked to cell membrane formation and transport function recovery of BECs in the late phase. In brief, comparative analysis of biological activities of BECs and the regenerating liver reveals that biological activities at the cellular level are not always consistent with those at tissue level, suggesting the necessity of cell level investigation on liver regeneration. Finally, expression of BEC markers in hepatocytes may suggest the potential of hepatocytes to transdifferentiate into BEC.