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Hepatic gene expression during liver regeneration in response to partial hepatectomy: late time points (24h, 38h, 48h)

ABSTRACT: The process of liver regeneration can be divided into a series of stages that include initial inductive or priming events through cellular mitosis. Following two-thirds liver resection, the liver undergoes the “priming” phase, in which cytokines TNF-a and IL-6 activate their respective receptors in hepatocytes. This leads to the activation of several key transcription factors: NF-kB, AP-1, Stat 3, Stat 1, and C/EBP-b and -d . These transcription factors induce the expression of immediate early genes. HGF is also expressed at this time and involved in the transition of quiescent hepatocytes into the G1 phase of the cell cycle. During the G1 phase, delayed early genes are expressed followed by induction of cell cycle–related genes, both of which require new protein synthesis for their production. Increased expression of FoxM1B and TGF-a occurs at the G1/S transition and is correlated with increased expression of cyclinD1 and decreased expression of cdk inhibitors. During the G2/M phase of the cell cycle, FoxM1B directly elevates cyclinB1, cyclinB2, and cdc25B expression. Additionally, FoxM1B is associated with increased cyclinF and p55cdc, which are involved in completion of the cell cycle following partial hepatectomy. In mice, two-thirds partial hepatectomy promotes proliferation of liver cells and rapid growth of the remaining liver tissue, resulting in complete restoration of organ mass in approximately 7 days (Mackey S. et al. Hepatology 2003 Dec;38(6):1349-52).

ORGANISM(S): Mus musculus

PROVIDER: GSE20426 | GEO | 2011/02/16

SECONDARY ACCESSION(S): PRJNA129821

REPOSITORIES: GEO

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Hepatic gene expression during liver regeneration in response to partial hepatectomy: late time points (24h, 38h, 48h)

Project description:The process of liver regeneration can be divided into a series of stages that include initial inductive or priming events through cellular mitosis. Following two-thirds liver resection, the liver undergoes the “priming” phase, in which cytokines TNF-a and IL-6 activate their respective receptors in hepatocytes. This leads to the activation of several key transcription factors: NF-kB, AP-1, Stat 3, Stat 1, and C/EBP-b and -d . These transcription factors induce the expression of immediate early genes. HGF is also expressed at this time and involved in the transition of quiescent hepatocytes into the G1 phase of the cell cycle. During the G1 phase, delayed early genes are expressed followed by induction of cell cycle–related genes, both of which require new protein synthesis for their production. Increased expression of FoxM1B and TGF-a occurs at the G1/S transition and is correlated with increased expression of cyclinD1 and decreased expression of cdk inhibitors. During the G2/M phase of the cell cycle, FoxM1B directly elevates cyclinB1, cyclinB2, and cdc25B expression. Additionally, FoxM1B is associated with increased cyclinF and p55cdc, which are involved in completion of the cell cycle following partial hepatectomy. In mice, two-thirds partial hepatectomy promotes proliferation of liver cells and rapid growth of the remaining liver tissue, resulting in complete restoration of organ mass in approximately 7 days (Mackey S. et al. Hepatology 2003 Dec;38(6):1349-52). Liver tissue was collected 0h, 24h, 38h, and 48h after partial hepatectomy or sham surgery from both young (5-6 months) and old (25-27 months) CB6F1 mice. All control and partial hepatectomy samples were assayed in triplicate. Relative gene expression levels were determined using Affymetrix moe430_2 oligo arrays.

2011-02-16 | E-GEOD-20426 | biostudies-arrayexpress

Hepatic gene expression during liver regeneration in response to partial hepatectomy: early time points (0.5h,1h,2h,4h)

Project description:The process of liver regeneration can be divided into a series of stages that include initial inductive or priming events through cellular mitosis. Following two-thirds liver resection, the liver undergoes the “priming” phase, in which cytokines TNF-a and IL-6 activate their respective receptors in hepatocytes. This leads to the activation of several key transcription factors: NF-kB, AP-1, Stat 3, Stat 1, and C/EBP-b and -d . These transcription factors induce the expression of immediate early genes. HGF is also expressed at this time and involved in the transition of quiescent hepatocytes into the G1 phase of the cell cycle. During the G1 phase, delayed early genes are expressed followed by induction of cell cycle–related genes, both of which require new protein synthesis for their production. Increased expression of FoxM1B and TGF-a occurs at the G1/S transition and is correlated with increased expression of cyclinD1 and decreased expression of cdk inhibitors. During the G2/M phase of the cell cycle, FoxM1B directly elevates cyclinB1, cyclinB2, and cdc25B expression. Additionally, FoxM1B is associated with increased cyclinF and p55cdc, which are involved in completion of the cell cycle following partial hepatectomy. In mice, two-thirds partial hepatectomy promotes proliferation of liver cells and rapid growth of the remaining liver tissue, resulting in complete restoration of organ mass in approximately 7 days (Mackey S. et al. Hepatology 2003 Dec;38(6):1349-52). Liver tissue was collected 0h, 0.5h, 1h, 2h, and 4h after partial hepatectomy or sham surgery from both young (5-6 months) and old (25-27 months) CB6F1 mice. All control and partial hepatectomy samples were assayed in triplicate. Relative gene expression levels were determined using Affymetrix Murine Genome U74 Version 2 Array.

2011-02-16 | E-GEOD-20425 | biostudies-arrayexpress

Hepatic gene expression during liver regeneration in response to partial hepatectomy: early time points (0.5h,1h,2h,4h)

2011-02-16 | GSE20425 | GEO

A Novel, Dynamic Pattern-based Analysis of NF-kappaB Binding During the Priming Phase of Liver Regeneration Reveals Switch-Like Functional Regulation

Project description:Following partial hepatectomy, a coordinated series of molecular events occurs to regulate hepatocyte entry into the cell cycle to recover lost mass. In rats during the first six hours following resection, hepatocytes are primed by a tightly controlled cytokine response to prepare hepatocytes to begin replication. Although it appears to be a critical element driving regeneration, the cytokine response to resection has not yet been fully characterized. Specifically, the role of one of the key response elements to cytokine signaling (NF-κB) remains incompletely characterized. In this study, we present a novel, genome-wide, pattern-based analysis characterizing NF-κB binding during the priming phase of liver regeneration. We interrogated the dynamic regulation of priming by NF-κB through categorizing NF-κB binding in different temporal profiles: immediate sustained response, early transient response, and delayed response to partial hepatectomy. We then identified functional regulation of NF-κB binding by relating the temporal response profile to differential gene expression. We found that NF-κB bound genes govern negative regulation of cell growth and inflammatory response immediately following hepatectomy. NF-κB also transiently regulates genes responsible for lipid biosynthesis and transport as well as induction of apoptosis following hepatectomy. By the end of the priming phase, NF-κB regulation of genes involved in inflammatory response, negative regulation of cell death, and extracellular structure organization became prominent. These results suggest that the immediate, transient, and delayed NF-κB signaling serve different functional transitions that drive the onset of regeneration.

2015-07-07 | GSE70522 | GEO

Effect of conditional deletion of S6 ribosomal protein following partial hepatectomy

2009-05-01 | GSE13864 | GEO

Survivin deficient liver of mice after partial hepatectomy

Project description:The liver possesses remarkable regenerative capacity in response to injury. Upon partial hepatectomy (PHx), terminally differentiated hepatocytes in the remaining liver enter the cell cycle and restore the liver mass and function within weeks. However, liver regeneration is often impaired in livers with chronic diseases. Survivin, an inhibitor of apoptosis protein (IAP) and member of chromosome passenger complex (CPC), plays versatile roles in cell mitosis and apoptosis. We and others found that the expression of Survivin was highly increased in liver during PHx-induced liver regeneration, which indicated that Survivin played important roles in this process. However, the function of Survivin in liver regeneration remains largely undefined. Here, using mice with genetic deletion of Survivin, we found that during PHx-induced liver regeneration Survivin regulated both hepatocyte G1/S phase transition by inhibiting the expression of p21 and G2/M phase transition by regulating the localization of CPC. Moreover, restoration of Survivin expression in Survivin-deficient hepatocytes inhibited p21 expression and promote both hepatocyte G1/S and G2/M transition during PHx-induced liver regeneration.

2017-01-01 | GSE83598 | GEO

RNA-seq transcriptonal profiling in partial hepatectomy liver tissues in Arid1a WT and liver specific KO mice.

Project description:Arid1a is the subunit of SWI/SNF complex, which was reported to guide SWI/SNF to DNA. Here, we found that loss of Arid1a in the liver results in improved liver regeneration after partial hepatectomy.Genome-wide analysis showed that after hepatectomy,loss of Arid1a reduces the recruitment and activity of E2F4 on target promoters, resulting in expression programs that favor regeneration during injury.RNAseq shows transcriptional profiling in WT and Arid1a LKO livers pre- and post-hepatectomy, which confirmed the E2F4 target genes and cell cycle genes were upregulated after hepatectomy. After partial hepatectomy, liver transcriptional profiling in WT and Arid1a liver specific KO mice were generated by RNA-seq analysis.

2016-03-30 | E-GEOD-76926 | biostudies-arrayexpress

Pharmacological Activation of Nrf2 Enhances Functional Liver Regeneration

Project description:The transcription factor Nuclear factor erythroid 2-related factor 2 (Nrf2) regulates an array of cytoprotective genes, yet studies in transgenic mice have led to conflicting reports on its role in liver regeneration. We aimed to test the hypothesis that pharmacological activation of Nrf2 would enhance liver regeneration. Wild type (WT) and Nrf2 null mice were administered bardoxolone methyl (CDDO-Me), a potent activator of Nrf2 that has entered clinical development, and then subjected to partial hepatectomy (PHx). CDDO-Me enhanced the rate of restoration of liver volume and improved liver function (multispectral optoacoustic imaging in wild type, but not Nrf2 null, mice following two-thirds partial hepatectomy. These effects were associated with an increase in hepatocyte hypertrophy and proliferation, the suppression of immune and inflammatory signals, and metabolic remodeling in the remnant liver tissue.

2021-04-22 | GSE169242 | GEO

Effect of conditional deletion of S6 ribosomal protein following partial hepatectomy

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 RNA was isolated from mouse livers at different time-points following partial hepatectomy. Conditional deletion of the RPS6 gene was perfomed by injecting polyinosinic-polycytidylic acid in mice harbouring a floxed version of the RPS6 gene and a cre recombinase under the regulation of an interferon responsive promoter (MX-CRE). The mice used a control have also a floxed version of the RPS6 gene but lack the cre recombinaste transgene.

2009-05-01 | E-GEOD-13864 | biostudies-arrayexpress

Partial hepatectomy 1, 2, 4, 6h

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)

2007-04-06 | GSE7415 | GEO

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