Similar Datasets
Project description:The liver is the only organ in mammals, which fully regenerates after injury. To identify novel regulators of liver regeneration, we performed quantitative large-scale proteomics analysis of subcellular fractions from normal versus regenerating mouse liver. Proteins of the ubiquitin-proteasome pathway were rapidly regulated by partial hepatectomy, with the ubiquitin ligase Nedd4-1 being among the top hits. Knock-down of Nedd4-1 in hepatocytes in vivo through nanoparticle-mediated delivery of siRNA caused severe liver damage after partial hepatectomy and impaired regeneration, resulting in liver failure. Mechanistically, we demonstrate that Nedd4-1 is required for efficient activation of Erk1/2 signaling by receptor tyrosine kinases involved in liver regeneration through inhibition of receptor internalization, thus controlling a major pro-mitogenic and cytoprotective signaling pathway in the regenerating liver. These results highlight the power of large-scale proteomics to identify key players in liver regeneration and the importance of posttranslational regulation of growth factor signaling in this process.
2017-09-13 | PXD004108 | Pride
Project description:The study examined the role of TNF alpha in regulation of liver regeneration. For this purpose animals were divided in three groups of healthy controls, 2/3 partial hepatectomy alone, and animals pretreated with TNF alpha antagonist followed by 2/3 partial hepatectomy. Liver regeneration responses were then examined in conjunction with gene expression analysis at the peak of partial hepatectomy induced DNA synthesis. Substantive differences were identified in multiple gene ontology groups and cellular events and processes to indicate that TNF alpha was deleterious for partial hepatectomy induced liver regeneration.
2020-07-01 | GSE77888 | GEO
Project description:Bile acid return from the intestine and attendant signaling is necessary for liver regeneration after partial hepatectomy or CCl4 injury Three groups of rat liver were examined at 4 time points (0, 4h, 12h, 24h) after partial hepatectomy; RNA from whole rat liver was isolated and deep sequencing was performed using the Illumina TruSeq platform
2014-02-05 | E-GEOD-54673 | biostudies-arrayexpress
Project description:Liver is uniquely capable to repair itself after injury. Multiple molecular and biochemical processes initiated after partial hepatectomy, lead to proliferation of all cells within the liver. MicroRNAs (miRNAs) are a class of highly abundant non-coding RNA molecules that cause post-transcriptional gene repression and are involved in several biological processes including cell cycle regulation and differentiation. We examined the expression levels of miRNAs in liver tissue received from control mice (L0) and compared them with the corresponding levels in liver tissue 12 hours after liver regeneration induced by 2/3 partial hepatectomy (L12). MicroRNA expression was investigated using microRNA profiling. Further qPCR analysis was used for validation of the differentially expressed microRNAs at an early stage of liver regeneration, induced by 2/3 partial hepatectomy. TargetScan and Gene Ontology (GO) analysis was performed in order to identify the possible miRNA target genes and their ontology, respectively. A subset of miRNAs were found to be differentially expressed during liver regeneration. Mmu-miR-21 and mmu-miR-30b* showed the higher levels of up-regulation in liver tissue from the hepatectomized mice at the end of the experiment (L12) compared to the sham operated mice (L0). Mmu-miR-21 up-regulation was further confirmed by qPCR. In situ hybridization (ISH) revealed that mmu-miR-21 exhibited the higher levels of expression at 12 hours post hepatectomy. On the contrary, mmu-miR-34c*, mmu-miR-144, mmu-miR-207, mmu-miR-207, mmu-miR-451, mmu-miR-582-3p and mmu-miR-290-5p exhibited <0.5 down-regulation in liver tissue after partial hepatectomy in L12 vs. L0 mice. Microarrays and qPCR results were in good agreement (Pearson correlation = 0.881). Our results provide important information regarding how microRNAs are deferentially expressed in murine liver tissue before and after partial hepatectomy. The early up-regulation of mmu-miR-21 during the process of liver regeneration suggests a regulatory role in liver regeneration in vivo. Twenty male wild type mice C57BL6J (8 weeks old) fed a standard diet were used for the liver regeneration experiment. Mice were housed in the animal facility of the University of Patras Medical School in temperature-, light- and humidity-controlled rooms with a 12-h light/dark cycle. All animal procedures were approved by the institutional review board of the University of Patras Medical School and were in accordance with EC Directive 86/609/EEC. A 2/3 partial hepatectomy (PH) was performed on 10 mice according to a recently published standardized protocol whereby the median and left lobes of the liver were removed and another 10 sham operated mice were used as the control group. The liver was allowed to regenerate and mice were sacrificed 12 hours after operation. Liver samples were collected from the sham operated mice (L0) and the hepatectomized mice at the end of the experiment (L12).
2012-01-18 | E-GEOD-35128 | biostudies-arrayexpress
Project description:Liver is uniquely capable to repair itself after injury. Multiple molecular and biochemical processes initiated after partial hepatectomy, lead to proliferation of all cells within the liver. MicroRNAs (miRNAs) are a class of highly abundant non-coding RNA molecules that cause post-transcriptional gene repression and are involved in several biological processes including cell cycle regulation and differentiation. We examined the expression levels of miRNAs in liver tissue received from control mice (L0) and compared them with the corresponding levels in liver tissue 12 hours after liver regeneration induced by 2/3 partial hepatectomy (L12). MicroRNA expression was investigated using microRNA profiling. Further qPCR analysis was used for validation of the differentially expressed microRNAs at an early stage of liver regeneration, induced by 2/3 partial hepatectomy. TargetScan and Gene Ontology (GO) analysis was performed in order to identify the possible miRNA target genes and their ontology, respectively. A subset of miRNAs were found to be differentially expressed during liver regeneration. Mmu-miR-21 and mmu-miR-30b* showed the higher levels of up-regulation in liver tissue from the hepatectomized mice at the end of the experiment (L12) compared to the sham operated mice (L0). Mmu-miR-21 up-regulation was further confirmed by qPCR. In situ hybridization (ISH) revealed that mmu-miR-21 exhibited the higher levels of expression at 12 hours post hepatectomy. On the contrary, mmu-miR-34c*, mmu-miR-144, mmu-miR-207, mmu-miR-207, mmu-miR-451, mmu-miR-582-3p and mmu-miR-290-5p exhibited <0.5 down-regulation in liver tissue after partial hepatectomy in L12 vs. L0 mice. Microarrays and qPCR results were in good agreement (Pearson correlation = 0.881). Our results provide important information regarding how microRNAs are deferentially expressed in murine liver tissue before and after partial hepatectomy. The early up-regulation of mmu-miR-21 during the process of liver regeneration suggests a regulatory role in liver regeneration in vivo.
2012-01-18 | GSE35128 | GEO
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.
2014-02-28 | GSE55434 | GEO
Project description:Identification of altered gene expression of normal and regenerating liver post partial hepatectomy Platform used - Affymetrix GeneChip Mouse Genome 430 2.0 Array
2021-01-01 | GSE110292 | GEO
Project description:This SuperSeries is composed of the following subset Series: GSE20425: Hepatic gene expression during liver regeneration in response to partial hepatectomy: early time points (0.5h,1h,2h,4h) GSE20426: Hepatic gene expression during liver regeneration in response to partial hepatectomy: late time points (24h, 38h, 48h) Refer to individual Series
2011-02-16 | E-GEOD-20427 | biostudies-arrayexpress
Project description:We studied the role of the post-translational modification called O-GlcNAcylation during liver regeneration. Here we generated O-GlcNAc transferase (OGT-KO) and O-GlcNAcase (OGA-KO) hepatocyte-specific knock-out mice. 70% partial hepatectomy (PHX) was performed to induce liver regeneration. We showed that OGA-KO mice had normal liver regeneration whereas OGT-KO mice had a defect in the termination of liver regeneration.
2022-02-25 | GSE188882 | GEO
Project description:Background and Aims: Although the liver can regenerate after sustaining injury, the tools to detect ongoing regeneration are lacking. The restoration of the liver after hepatectomy involves rapid, sequential, and coordinated changes in gene expression that result in systemic and local changes, such as the activation of progenitor cell populations and proliferation of quiescent hepatocytes. We postulated that changes in gene expression and regenerative programs could be activated within target cells through the transfer of extracellular RNA across cells or within the circulation, coordinating tissue response, and these extracellular RNA could represent biomarkers of the hepatic regenerative response. Methods: We identified temporal changes in circulating extracellular RNA at selected time periods up to 24 hours after partial hepatectomy in mice. (CD-1 males) Results: A peak increase in extracellular RNA content occurred 6 hours after hepatectomy. RNA sequencing was performed to identify the circulating extracellular non-coding RNA released after partial hepatectomy. To identify candidate markers, we used bioinformatics analyses to find the enriched RNA in the circulation after hepatectomy. We then performed tissue expression analysis for selected non-coding RNA and correlated it to these findings. Finally, a digital PCR assay was used to detect and quantify the expression of selected extracellular RNA in serum samples. Conclusions: Extracellular RNA that were selectively enriched during acute regeneration were detected within the circulation and represent biomarkers of ongoing liver regeneration in mice. The ability to detect ongoing active regeneration would benefit the evaluation of hepatic recovery after liver injury.
2019-01-20 | GSE77045 | GEO