Project description:RNA-seq analysis was performed in samples from WT and NOX4 Knock-out mice after two-thirds Partial Hepatectomy (PH). Transcriptomic analysis through RNA-seq revealed significant changes mainly 24 hours after PH in NOX4-/- mice and support a relevant role for Myc in a node of regulation of proliferation-related genes.
Project description:Background: Extended hepatectomies may result in post-hepatectomy liver failure, a condition with a high mortality. The main purpose of the present study was to investigate and compare the gene expression profiles in rats subjected to increasing size of partial hepatectomy. Methods: 40 Wistar rats were subjected to 30%, 70%, or 90% partial hepatectomy, sham operation or no operation. 24 hours following resection, liver tissue was harvested and genome-wide expression analysis was performed. Results: Cluster analysis revealed 2 main groupings, one containing the PH(90%) and one containing the remaining groups (baseline, sham, PH(30%) and PH(70%)). Categorization of specific affected molecular pathways in the PH(90%) group revealed a downregulation of cellular homeostatic functions degradation and biosynthesis, whereas proliferation, cell growth, and cellular stress and injury were upregulated in the PH(90%) group. After PH(90%), the main upregulated pathways were mTOR and ILK. The main activated upstream regulators were hepatocyte growth factor and transforming growth factor. Conclusion: With decreasing size of the future liver remnant, the liver tended to prioritize expression of genes involved in cell proliferation and differentiation at the expense of genes involved in metabolism and body homeostasis. This prioritizing may be an essential molecular explanation for post-hepatectomy liver failure.
Project description:Six rats underwent partial hepatectomy (PH) (3, 1/3PH; 3, 2/3PH). The total mRNA of three rats each group were pooled and compared by microarray to selected the mRNA which differs between between 2/3PH with robust DNA replication and 1/3PH with a minimal replicative response.
Project description:We investigated by microarray analysis the expression pattern of hepatic genes in young and old untreated mice and the differences in gene expression profile following surgical partial hepatectomy (2/3 PH).
Project description:Adult hepatocytes are quiescent cells, that can be induced to proliferate in response to a reduction in liver mass (liver regeneration) or by agents endowed with mitogenic potency (primary hyperplasia). The latter condition is characterized by a more rapid entry of hepatocytes into the cell cycle but the mechanisms responsible for the accelerated entry into the S phase are unknown. Illumina microarray was used to profile mRNA expression in CD-1 mice livers 1, 3 and 6 hours after 2/3 partial hepatectomy (PH) or a single dose of TCPOBOP, a ligand of the constitutive androstane receptor. Ingenuity pathway and DAVID analyses were performed to identify deregulated pathways
Project description:Liver regeneration has important implications because many therapeutic strategies for the surgical treatment of liver diseases, such as removal of liver tumors and liver transplantation, depend on the ability of the liver to regenerate physically and functionally. Recent studies reported that lncRNAs control cell proliferation in hepatocellular carcinoma (HCC). However, the role of lncRNAs in liver regeneration and the overall mechanisms remain largely unknown. To address this issue, we carried out a genome-wide lncRNA microarray analysis during liver regeneration in mice after 2/3 partial hepatectomy (PH) at various time points. The results revealed differential expression of thousands of lncRNAs during liver regeneration. Six-week-old male wildtype C57Bl/6 mouse liver samples were obtained at 0, 1.5, 12, and 24 hours after 2/3 PH, and three mice were analyzed for each time point. Total RNA was isolated using Trizol.Mouse Stringent LncRNA Array (4 x 44K, ArrayStar, Rockville, MD) were used to monitor the expression level of approximately 14000 lncRNAs identified from the NCBI RefSeq, UCSC, RNAdb2.0, NRED, Fantom3.0 and UCRs. LncRNAs differentially expressed were identified by comparing expression levels during liver regeneration in mice after 2/3 partial hepatectomy (PH) at various time points.
Project description:We report the results of AcH3K9 ChIP-Seq on regenerating liver harvested 12 h after partial hepatectomy (PH) from mice treated with supplemental parenteral dextrose (to delay onset of PH-induced hypoglycemia) or vehicle (as control).
Project description:Autonomic nervous system is widely distributed in liver, and some reserchers have found that disruppted autonomic nerves will delay liver regeneration. We used microarrays to further highlight the regulatory role of autonomic nervous system in liver regeneration at gene transcription level. Surgical operations of rat partial hepatectomy (PH) and its operation control (OC), sympathectomy combining partial hepatectomy (SPH), vagotomy combining partial hepatectomy (VPH), and total liver denervation combining partial hepatectomy (TDPH) were performed, and the expression profiles of regenerating liver at 2h were detected using Rat Genome 230 2.0 array. Then the significantly changed genes related to liver regeneration (LR)-, injury-, splanchnic nerve-LR-, vagal nerve-LR-, and autonomic nerve-LR-related genes were identified, respectively. The relevance of gene expression profiles and biological processes was analyzed by bioinformatics and systems biology.