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

        Cunshuan Xu,Xiaoguang Chen,Cuifang Chang,Gaiping Wang,Wenbo Wang,Lianxing Zhang,Qiushi Zhu,Lei Wang,Fuchun Zhang 한국유전학회 2012 Genes & Genomics Vol.34 No.3

        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 bio-logical 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.

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        Analysis of Gene Expression Profiles of Liver Stellate Cells During Liver Regeneration in Rats

        Xu Cunshuan,Chen Xiaoguang,Chang Cuifang,Wang Gaiping,Wang Wenbo,Zhang Lianxing,Zhu Qiushi,Wang Lei,Zhang Fuchun 한국분자세포생물학회 2011 Molecules and cells Vol.31 No.1

        This study performed a large-scale, high-throughput analy-sis of transcriptional profiling of liver stellate cells (LSCs) at the cellular level to investigate changes in the biological activity of LSCs during rat liver regeneration (LR) and the relation of these changes to LR. First, a rat liver regeneration model was established by partial hepatectomy (PH). Stellate cells were isolated in high purity and yield from the regenerating rat liver by Percoll density gradient centrifugation and immunomagnetic bead sorting. The changes in gene expression of LSCs after PH were examined using a rat genome 230 2.0 array composed of 24622 genes. The results indicated that 10241 of the 24622 genes investigated on the array were differentially expressed in LSCs. Of the 10241 genes, 1563 known genes were related to LR, which were grouped into three major gene expression clusters according to three-fold cut-off threshold: the up-regulated gene cluster, the down-regulated gene cluster, and the cluster composed of genes showing complex changes in expression. Additionally, the genes were grouped into those involved in transcription regulation, signal transduction, transport, cellular metabolism, in-flammation and immunity by functional analysis. When gene expression profiles were combined with the results of gene functional analysis, most of the genes involved in cytokine secretion and retinol metabolism in LSCs were significantly enriched in the cluster characterized by decreased expression, whereas genes involved in lipid metabolism were mostly enriched in the cluster showing increased expression. Based on further analysis of genes expressed in a phase-dependent manner during LR, it was suggested that lipid metabolism in LSCs was enhanced in the whole regeneration process, and that immune response and cytokine secretion were impaired during all three regenerative phases.

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