Comparison of hepatic gene change after partial hepatectomy
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ABSTRACT: Partial hepatectomy, resection of a portion of liver mass, indues significant liver regenerative responses that consist of numerous genetic changes. To identify specific genetic changes, we compare the liver of mice underwent either hepatectomy or sham operation.
Project description:Partial hepatectomy, resection of a portion of liver mass, indues significant liver regenerative responses that consist of numerous genetic changes. To identify specific genetic changes, we compare the liver of mice underwent either hepatectomy or sham operation. The experiment compared 2 sets of biological duplicates which included hepatectomized liver and sham-operated liver
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:Despite being the standard of care for patients with Stage IV colorectal cancer (CRC), the effects of a resection of liver metastasis on the metastatic disease are poorly understood. To elucidate the influence of surgical metastasectomies on metastasized CRC, we investigated the cellular and molecular effects of partial hepatectomy in a mouse model of orthograde CRC liver metastasis.
Project description:4 Adult male Sprague-Dawley rats (275-350 g) were anesthetized and subjected to hepatectomy sham surgery (abdominal cavity was opened, liver was handled, but no tissue resection was made). 1 hour after the surgery rats were killed and liver samples were harvested. This study was conducted to analyzes the effects of surgical stress on gene expression levels in rat liver. It provides additional data to 1-6 h partial hepatectomy study (Series GSE7415). Keywords: 1h hepatectomy sham surgery
Project description:Krüppel-like factor 6 (KLF6) is a transcription factor and tumor suppressor. Loss or reduction of KLF6 is linked with progression of experimental and human hepatocellular carcinoma. Despite its important contributions to liver homeostasis and growth, there are no data characterizing the involvement of KLF6 to hepatic regeneration. Microarray data from wildtype and DeltaKlf6 mice were used to identify regulating mechanisms and potential mediators within liver regeneration Wildtype and hepatocyte specific Klf6 knockout mice (DeltaKlf6) were employed for 70% partial liver resection/hepatectomy (PHx) in order to analyse liver regeneration. Twelve hours after partial hepatectomy animals were scrificed and remnant liver tissue was used for further experiemnts. For the overall study we used 6 animals per group, and included RNA from liver tissue of 3 wildtype and 3 DeltaKlf6 animals for the microarray analysis. Wildtype animals were used as controls.
Project description:The cellular and molecular mechanisms involved in liver regeneration following partial hepatectomy (PHx) are complicated. Liver sinusoidal endothelial cells (LSECs) play key roles in orchestrating liver regeneration, especially during the inductive phase and angiogenic phase post PHx (from day 0 to day 8). However, the expression profile of LSECs during the late phase of regeneration remains poorly explored. Thus, we purified LSECs from mice underwent PHx or sham operation at day 14 to unravel their transcriptome changes in the late phase of liver regeneration.
Project description:To investigate the function of MKL1 in liver regeneration. Wild-type C57/B6 mouse were performed sham operation or two-thirds hepatectomy. 24 hours later, ChIP-seq was did with MKL1 antibody.
Project description:The recovery of liver mass is mainly mediated by proliferation and enlargement of hepatocytes after partial hepatectomy. Studying the gene expression profiles of hepatocytes after partial hepatectomy will be helpful in exploring the mechanism of liver regeneration. We used microarrays to further highlight the regulatory role of hepatocyte in liver regeneration at gene transcription level.
Project description:Deletion of the RPS6 gene in mouse liver results in the inhibition of 40S ribosome biogenesis and the failure of hepatocytes to enter S-phase following partial hepatectomy. This microarray experiment was designed to assess the effects of RPS6 deletion on the expression of genes involved in liver regeneration following partial hepatectomy. Keywords: time course, liver
Project description:Adult male Sprague-Dawley rats (275-350 g) were anesthetized and subjected to two-thirds PHx. Liver sections removed by partial hepatectomy (PHx) were collected and used both as controls (time=0) and as individual reference material for each animal to reduce the error introduced by animal-to-animal variability. At 1, 2, 4, and 6 hours following PHx, rats were killed and liver samples were harvested. Keywords: Time series PHx (1, 2, 4, 6h)