Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Pharmacological Activation of Nrf2 Enhances Functional Liver Regeneration

ABSTRACT: 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE169242 | GEO | 2021/04/22

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

miRNA expression during liver regeneration in the chronic ethanol-fed rat

Project description:miRNA expression was profiled before and during liver regeneration following 2/3 partial hepatectomy (PHx) in chronic ethanol-fed (EtOH) and pair-fed carbohydrate control (CHO) rats. Prior to PHx, EtOH animals were fed a liquid diet containing 36% of the calories from ethanol for 5 weeks. Left lateral and medial (LLM) lobes were removed at time of PHx and used as t = 0 biological controls. Remnant liver tissue (PHx) was harvested 1 h, 6 h, 12 h, and 24 h after PHx. RNA from 4 biological replicates was pooled for profiling miRNA expression on Agilent Rat miRNA Microarrays v1.0. miRNA expression was profiled in the chronic ethanol-fed (EtOH) and carbohydrate control pair-fed (CHO) liver prior to (LLM) and 1 h, 6 h, 12 h, and 24 h after partial hepatectomy (PHx).

2012-07-22 | E-GEOD-34057 | biostudies-arrayexpress

Expression in liver tissue of wildtype (wt) or hepatocyte specific Klf6 knockout (DeltaKLF6) after partial hepatectomy

Project description:KrÃ¼ppel-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.

2016-08-10 | E-GEOD-85381 | biostudies-arrayexpress

RNA-sequence data of mouse liver sinusoidal endothelial cells on day 14 after partial hepatectomy (PHx) or sham operation

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.

2021-08-06 | GSE181482 | GEO

Transcription profiling of human liver shortly after partial hepatectomy (PHx)

Project description:The liver has a remarkable ability to regenerate, with the best experimental model for regeneration being partial hepatectomy (PHx), in which up to two-thirds of the liver may be removed, and the residual lobes enlarge to make up for the missing mass in a few days’ time. Liver regeneration has been extensively studied, mainly in rodent models, and characterized in terms of transcriptional regulation of gene expression. However, little is known regarding regulation of gene expression in a human model of regeneration following PHx. We used microarrays to follow gene expression changes shortly following PHx. Experiment Overall Design: Liver tissues were collected from patients undergoing a PHx surgery (1.5, 42 and 81 years) under an IRB approval, at the onset (T0) and shortly after PHx (0.5hr, 1hr and 1.5hrs) for RNA extraction and hybridization on Affymetrix microarrays.

2009-10-10 | E-GEOD-15239 | biostudies-arrayexpress

Gene expression in the chronic ethanol-treated rat liver during liver regeneraiton

Project description:In this study, we analyzed the effects of chronic alcohol consumption on liver repair and regeneration after partial hepatectomy (PHx). Rats were fed a liquid diet containing 36% of total calories derived from ethanol for 5 weeks; corresponding pair-fed calorie-matched controls were fed diets in which ethanol calories were replaced either by carbohydrate or by fat. After 5 weeks, rats were subjected to 70% PHx and liver samples were collected at 1, 6 and 24h after the surgery. The excised liver samples at t=0 served as within-animal controls. We used Affymetrix Rat Gene 1.0 ST arrays to obtain global gene expression data from each liver sample (n=4 replicate rats, 72 arrays total). Gene expression was profiled in the chronic ethanol-fed (EtOH) and carbohydrate control pair-fed (CHO) liver prior to (control) and 1 h, 6 h, 12 h, and 24 h after partial hepatectomy (PHx).

2012-07-23 | E-GEOD-33785 | biostudies-arrayexpress

ACUTE BLEEDING AND STORED RED BLOOD CELLS TRANSFUSION ATTENUATES LIVER REGENERATION FOLLOWING PARTIAL HEPATECTOMY

Project description:Our aim was to study the impact of bleeding and red blood cell (RBC) resuscitation on liver regeneration. We assessed the impact of RBC storage time on liver regeneration following 50% partial hepatectomy (PHx) in rats, and explored possible contributing molecular mechanisms using immunohistochemistry, RNA-Seq, and macrophage depletion.

2022-11-14 | GSE216924 | GEO

Transcription profiling of mouse Nrf2 knockout caused by ROS-mediated insulin/IGF-1 resistance

Project description:The liver is frequently challenged by surgery-induced metabolic overload, viruses, or toxins, which induce the formation of reactive oxygen species. To determine the effect of oxidative stress on liver regeneration and to identify the underlying signalling pathways, we studied liver repair in mice lacking the Nrf2 transcription factor. In these animals, expression of several cytoprotective enzymes was reduced in hepatocytes, resulting in oxidative stress. As a consequence, tissue damage was aggravated, and liver regeneration after partial hepatectomy was delayed. Using in vitro and in vivo studies we identified oxidative stress-induced insulin/insulin-like growth factor resistance as the underlying mechanism. This deficiency impaired the activation of p38 mitogen-activated kinase, Akt kinase, and downstream targets after hepatectomy, resulting in enhanced death and delayed proliferation of hepatocytes. Our results reveal novel roles of Nrf2 in the regulation of growth factor signalling and in tissue repair. In addition, they provide new insight into the mechanisms underlying oxidative stress-induced defects in liver regeneration and thus offer new avenues to improve regeneration in patients with acute or chronic liver damage. Experiment Overall Design: Livers from Nrf2 k.o. and wt mice; 3 hybridizations per genoype: RNA samples were pooled from 3 individual animals

2008-06-16 | E-GEOD-8969 | biostudies-arrayexpress

Regulation of Liver Regeneration by Hepatocyte O-GlcNAcylation in Mice

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

Expression data from human livers shortly following partial hepatectomy (PHx)

2009-10-01 | GSE15239 | GEO

Analysis of the role of miR-21 in liver regeneration after partial hepatectomy (PHx) in chronic ethanol-treated rats through in vivo inhibition using LNAs

Project description:In this study, we analyzed the role of miR-21 in liver regeneration after partial hepatectomy (PHx) in chronic ethanol-treated rats. Male Sprague-Dawley rats were fed a liquid diet containing 36% of total calories derived from ethanol for 5 weeks; corresponding pair-fed calorie-matched controls were fed diets in which ethanol calories were replaced by carbohydrate. After 5 weeks, locked nucleic acid (LNA)-modified oligo antisense to miR-21 (AM21, Exiqon, Vedbaek, Denmark) was used to inhibit miRNA in vivo, and rats were subjected to 70% PHx. Liver samples were collected at 24h after the surgery. The excised liver samples at t=0 served as within-animal controls. Rat Gene 2.0 ST (Affymetrix, Santa Clara, CA) arrays were used to obtain global gene expression data from pooled liver samples (pools of 3 or 4 biological replicates/array, total 8 arrays). Gene expression was profiled in AM21 treated or untreated chronic ethanol-fed (EtOH) and carbohydrate control pair-fed (CHO) rat liver prior to (control, t=0) and 24 h after 70% partial hepatectomy (PHx).

2015-09-01 | E-GEOD-67242 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data