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Distribution of pteroylglutamates in rat liver during regeneration after partial hepatectomy.

ABSTRACT: 1. Liver pteroylpolyglutamate distribution was studied during regeneration after partial hepatectomy in rats maintained under controlled feeding conditions. 2. Pteroylhexaglutamate, pteroylpentaglutamate and pteroyltetraglutamate concentrations decrease from 12 to 72 h after operation, then increase and reach normal values at 180 h. Pteroyltriglutamate concentration, already high at 12 h, remains so in the subsequent periods. Pteroyldiglutamate concentration was unchanged. Monoglutamate concentrations at first decrease, and at 180 h exceed normal values. 3. The decrease in polyglutamate derivatives with a high number of glutamate residues, at present considered to be the coenzyme forms of folate, could be related not to a decreased synthesis, but to a greater requirement for these compounds during the early periods of regeneration, when biosynthetic processes are markedly increased. It is indeed probable that the increased availability of the preferred substrate of pteroylpolyglutamate synthetase, i.e. tetrahydrofolate, enhances conversion of folate into coenzyme forms.

SUBMITTER: Marchetti M

PROVIDER: S-EPMC1161901 | biostudies-other | 1980 May

REPOSITORIES: biostudies-other

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ATP release after partial hepatectomy regulates liver regeneration in the rat.

Project description:Background & aimsParacrine interactions are critical to liver physiology, particularly during regeneration, although physiological involvement of extracellular ATP, a crucial intercellular messenger, remains unclear. The physiological release of ATP into extracellular milieu and its impact on regeneration after partial hepatectomy were investigated in this study.MethodsHepatic ATP release after hepatectomy was examined in the rat and in human living donors for liver transplantation. Quinacrine was used for in vivo staining of ATP-enriched compartments in rat liver sections and isolated hepatocytes. Rats were treated with an antagonist for purinergic receptors (Phosphate-6-azo(benzene-2,4-disulfonic acid), PPADS), and liver regeneration after hepatectomy was analyzed.ResultsA robust and transient ATP release due to acute portal hyperpressure was observed immediately after hepatectomy in rats and humans. Clodronate liposomal pre-treatment partly inhibited ATP release in rats. Quinacrine-stained vesicles, co-labeled with a lysosomal marker in liver sections and isolated hepatocytes, were predominantly detected in periportal areas. These vesicles significantly disappeared after hepatectomy, in parallel with a decrease in liver ATP content. PPADS treatment inhibited hepatocyte cell cycle progression after hepatectomy, as revealed by a reduction in bromodeoxyuridine incorporation, phosphorylated histone 3 immunostaining, cyclin D1 and A expression and immediate early gene induction.ConclusionExtracellular ATP is released immediately after hepatectomy from hepatocytes and Kupffer cells under mechanical stress and promotes liver regeneration in the rat. We suggest that in hepatocytes, ATP is released from a lysosomal compartment. Finally, observations made in living donors suggest that purinergic signalling could be critical for human liver regeneration.

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Expression data from rat liver tissue during liver regeneration after partial hepatectomy.

Project description:The liver has extraordinary powers of regeneration after partial hepatectomy (PH). Changes of gene expression play a key role in cell proliferation and differentiation during liver regeneration (LR). To understand the molecular mechanisms underlying LR, this study was designed to assess the changes of rat hepatic gene expression in a timely manner. We used microarrays to further highlight the regulatory role of rat liver tissue in liver regeneration at gene transcription level.

2014-12-02 | GSE63742 | GEO

Folate metabolism in the rat liver during regeneration after partial hepatectomy.

Project description:1. Folate metabolism was studied during the early phases of liver regeneration after partial hepatectomy in rats accustomed to eating during the first 8h of a daily 12h dark period. 2. The content of 5-CH(3)-H(4)folate was drastically decreased during the first hours of regeneration. 3. The total HCO-H(4)folate coenzymes showed a constant decrease during the first 3 days of regeneration, and a continuous interconversion between 5-HCO-H(4)folate and 10-HCO-H(4)folate. 4. 10-HCO-H(4)folate synthetase, serine hydroxymethyl-transferase and 5,10-CH(2)-H(4)folate dehydrogenase activities were relatively low during the first hours after the operation, and increased only several hours later. 5. The increase in enzyme activities showed a stepwise pattern, apparently due to an interaction between the regeneration process and the controlled feeding schedules.

| S-EPMC1172464 | biostudies-other

Expression data from rat hepatocyte during liver regeneration after partial hepatectomy

2014-02-28 | GSE55434 | GEO

Expression data from rat hepatocyte during liver regeneration after partial hepatectomy

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. Rat liver regeneration after partial hepatectomy (PH) is a good model to study the regulation of cell proliferation. We isolated hepatocytes from regenerating liver at 9 time points (2, 6, 12,24, 30, 36, 72, 120, and 168h) after PH and measured gene expression profiles of hepatocytes from 2h to 168h with rat Genome 230 2.0 gene chip. Each sample corresponding to one time point was hybridized onto one array. The experiment was repeated 3 times for each time point. In total, 10 time points were measured and 0h was used control group. After careful quality control analyses of each chip, Affymetrix GCOS 2.0 software was used to analyze the data. The relevance of gene expression profiles and biological processes was analyzed by bioinformatics and systems biology.

2014-02-28 | E-GEOD-55434 | biostudies-arrayexpress

Decellularized liver scaffolds promote liver regeneration after partial hepatectomy.

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Partial Hepatectomy Induced Long Noncoding RNA Inhibits Hepatocyte Proliferation during Liver Regeneration.

Project description:Liver regeneration after partial hepatectomy (PHx) is a complex and well-orchestrated biological process in which synchronized cell proliferation is induced in response to the loss of liver mass. To define long noncoding RNAs (lncRNAs) that participate in the regulation of liver regeneration, we performed microarray analysis and identified more than 400 lncRNAs exhibiting significantly altered expression. Of these, one lncRNA, LncPHx2 (Long noncoding RNA induced by PHx 2), was highly upregulated during liver regeneration. Depletion of LncPHx2 during liver regeneration using antisense oligonucleotides led to a transient increase in hepatocyte proliferation and more rapid liver regeneration. Gene expression analysis showed that LncPHx2 depletion resulted in upregulation of mRNAs encoding proteins known to promote cell proliferation, including MCM components, DNA polymerases, histone proteins, and transcription factors. LncPHx2 interacts with the mRNAs of MCM components, making it a candidate to regulate the expression of MCMs and other genes post-transcriptionally. Collectively, our data demonstrate that LncPHx2 is a key lncRNA that participates in a negative feedback loop modulating hepatocyte proliferation through RNA-RNA interactions.

| S-EPMC4514479 | biostudies-literature

In silico analysis of expression data during the early priming stage of liver regeneration after partial hepatectomy in rat.

Project description:The priming stage is the first step of liver regeneration (LR). This stage is characterized by the transition from G0 to cell cycle for 4 hours in rat. In this study, individual gene level and gene set level (GSEA) was performed to identify the candidate genes and significantly changed biological processes at 2 h after partial hepatectomy (PH). The leading edge analysis is performed to identify the key genes and iRegulon was employed for transcription factor (TF) analysis. A total of 53 differentially expressed genes were identified using RMA package based on R language at 2 h after PH, including the transcription factor, enzyme and cytokine. As the most important genes in our analysis, Socs3 was selected with a special analysis so as to find the pathways correlate to the expression of it. The changed significantly pathways in LR involved response to stress, ATP metabolism, and regulation of cell cycle mainly. Several transcription factors were identified including Stat5a, Cnot3 and zfp384. Taken together, at the early priming stage of LR in rat, the liver is experiencing some changes including response to stress, activated ATP metabolism and inhibition of cell cycle. Our analysis provided a detailed and comprehensive map for further research of the early priming stage of LR in rat.

| S-EPMC5837750 | biostudies-literature

Gene expression during the priming phase of liver regeneration after partial hepatectomy in mice.

Project description:Understanding the gene-expression patterns during liver regeneration may help to reveal how regenerative processes are initiated and controlled as well as shed new light onto processes that lead to liver disease. Using high-density oligonucleotide arrays, we have examined the gene-expression program in the livers of mice after partial hepatectomy. A time course was constructed for gene expression between 0 and 4 h after partial hepatectomy, corresponding to the priming phase of liver regeneration. The genomic program for liver regeneration involves transcription-factor generation, stress and inflammatory responses, cytoskeletal and extracellular matrix modification, and regulation of cell-cycle entry. The genome-wide changes that are observed provide a detailed and comprehensive map of the initial priming stage of liver regeneration.

| S-EPMC123230 | biostudies-literature

The Contribution of Hepatic Macrophage Heterogeneity during Liver Regeneration after Partial Hepatectomy in Mice.

Project description:MethodsIn the present study, we investigated hepatic macrophage heterogeneity in murine liver regeneration after 2/3 PHx through immunofluorescence staining, fluorescence-activated cell sorting analysis, and quantitative reverse transcription-polymerase chain reaction.ResultsOur research showed that Kupffer cells reduced rapidly in the early PHx and restored gradually depending on local proliferation and replenishment from infiltrating monocyte-derived macrophages. The ratio of ly6Chi to ly6Clo subset of macrophages in the liver changed dynamically, and hepatic macrophage function exhibits a significant difference in different stages of liver regeneration. Moreover, blocking infiltrating monocyte-derived macrophage recruitment augmented Kupffer cell proliferation but impaired the restoration of the hepatic macrophage pool, which led to delayed hepatocyte mitosis and liver regeneration.ConclusionsOur data suggest that hepatic macrophage changes dynamically in origin and function during liver regeneration following PHx and macrophage-targeted liver regeneration should consider macrophage heterogeneity.

| S-EPMC9568332 | biostudies-literature

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