Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

MCLR-elicited hepatic fibrosis and carcinogenic gene expression changes persist in rats with diet-induced nonalcoholic steatohepatitis through a 4-week recovery period

ABSTRACT: Nonalcoholic steatohepatitis (NASH) causes liver extracellular matrix (ECM) remodeling and is a risk factor for fibrosis and hepatocellular carcinoma (HCC). Microcystin-LR (MCLR) is a hepatotoxin produced by fresh-water cyanobacteria that causes a NASH-like phenotype, liver fibrosis, and is also a risk factor for HCC. The focus of the current study was to investigate and compare hepatic recovery after cessation of MCLR exposure in healthy versus NASH animals. Male Sprague-Dawley rats were fed either a control or a high fat/high cholesterol (HFHC) diet for eight weeks. Animals received either vehicle or 30 µg/kg MCLR (i.p: 2 weeks, alternate days). Animals were euthanized at one of three time points: at the completion of the MCLR exposure period and after 2 and 4 weeks of recovery. Histological staining suggested that after four weeks of recovery the MCLR-exposed HFHC group had less steatosis and more fibrosis compared to the vehicle-exposed HFHC group and MCLR-exposed control group. RNA-Seq analysis revealed dysregulation of ECM genes after MCLR exposure in both control and HFHC groups that persisted only in the HFHC groups during recovery. After 4 weeks of recovery, MCLR hepatotoxicity in pre-existing NASH persistently dysregulated genes related to cellular differentiation and HCC. These data demonstrate impaired hepatic recovery and persistent carcinogenic changes after MCLR toxicity in pre-existing NASH.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE188231 | GEO | 2021/11/06

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Changes of hepatic gene expression in C57BL/6N male mice fed high-fat high-calorie fructose (HFHC) diet for 8 weeks

Project description:In murine NAFL/NASH models, high-fat high-calorie fructose (HFHC) diet fed for 16 weeks induces hepatic steatosis, inflammatory cells infilatration and early stage fibrosis. In addition, HFHC diet 16 weeks but not 8 weeks is accompanied with weight gain and insulin resistance. The aim of this study is to determine the gene expression changes in mouse liver by HFHC diet for 8weeks.

2021-12-08 | GSE154426 | GEO

Hepatic transcriptomic changes during non-alcoholic steatohepatitis (NASH)-associated liver carcinogenesis in mice

Project description:Hepatocellular carcinoma (HCC), which accounts for 90% of all primary livers tumors, is the fourth most common cancer in the world. The development of HCC is a long-term and complex process, and uncovering the molecular mechanisms associated with HCC development is critical for the disease diagnosis, prevention, and treatment. Exploring these mechanisms using human HCC samples is desirable, but frequently impractical, with a number of limitations and shortcomings. The STAMTM (Stelic Institute & Co, Tokyo, Japan) mouse model of NASH-associated liver carcinogenesis is considered a useful and relevant model for investigating the molecular pathogenesis of NASH-derived HCC. This model resembles the human HCC development associated with progression from simple steatosis to NASH, fibrosis, and HCC. In the present study, by using high-throughput whole genome microarrays (SurePrint G3 Mouse Gene Expression v2, 8x60K; Agilent Technologies, Santa Clara, CA), we examined the transcriptomic profiles in the livers of STAMTM mice at different stages of liver carcinogenesis, including steatosis (6 week time interval), NASH (8 weeks), fibrotic stage (12 weeks), and in full-fledged HCC (20 weeks). The results of microarray analyses showed significant progressive changes in hepatic gene expression during the development of HCC. A total of 970, 1462, 2742, and 2857 of differentially expressed genes were identified in the livers at 6, 8, 12, and 20 weeks, respectively. Detailed analysis of these differentially expressed genes will benefit the understanding of the underlying mechanisms of non-alcoholic fatty liver disease-derived HCC. Transcriptomic profile in the liver of STAM mice at 6 weeks (steatosis; n=3), 8 weeks (steatohepatitis; n=3) 12 weeks (fibrosis; n=4) and 20 weeks (HCC-stage tumor tissue, n=4) weeks. Age-matched control samples were also analyzed.

2016-06-22 | E-GEOD-83596 | biostudies-arrayexpress

Dietary cholesterol promotes fatty liver-associated liver cancer by inducing aberrant genomic expression and mutations

Project description:We investigated the effects of cholesterol on nonalcoholic steatohepatitis (NASH) and hepatocellular carcinoma (HCC) in diethylnitrosamine-injected mice fed high-fat high-cholesterol (HFHC) diet versus high-fat (HF) alone. mRNA microarray analysis was applied for expressional aberrations.

2018-09-27 | E-MTAB-6002 | biostudies-arrayexpress

Gene expression profiles of livers and liver tumors from mice fed high-fat diet and high fructose-glucose solution for 52 weeks

Project description:The lack of a preclinical model of nonalcoholic steatohepatitis (NASH) and hepatocellular cancer (HCC) that recapitulates human disease is a major barrier to therapeutic development. We report a high fat-high sugar diet-induced NASH and HCC in a stable isogenic 129S1/SvImJ crossed with C57Bl/6J mice. Following diet initiation, there was sequential development of steatosis (4-8 weeks), steatohepatitis with ballooning and Mallory-Denk bodies (12-16 weeks), progressive fibrosis (16 week onwards) and spontaneous HCC (32-52 weeks). The mice developed obesity, insulin resistance and dyslipidemia. There was concordance with the human NASH transcriptome (FDR 0.001) with activation of lipogenic, inflammatory and apoptotic pathways relevant in humans. The HCC gene signature resembled S1 and S2 human HCC subclass (FDR 0.01 for both). This simple model of NASH and HCC that resembles human disease in terms of its triggers, physiological and biochemical parameters, histology, transcriptomic profile, and outcomes can facilitate preclinical development for these conditions. 129S1/SvImJ;C57Bl/6J (129/B6) mice were fed with high-fat diet (Western Diet) and high fructose-glucose solution (Sugar Water) (WD SW) or chow diet (CD) for 52 weeks, and total RNA samples were isolated from liver and tumor tissues for genome-wide expression profiling.

2016-07-25 | E-GEOD-67679 | biostudies-arrayexpress

Gene expression profiles of livers from mice fed high-fat diet and high fructose-glucose solution for 8 weeks

Project description:The lack of a preclinical model of nonalcoholic steatohepatitis (NASH) and hepatocellular cancer (HCC) that recapitulates human disease is a major barrier to therapeutic development. We report a high fat-high sugar diet-induced NASH and HCC in a stable isogenic 129S1/SvImJ crossed with C57Bl/6J mice. Following diet initiation, there was sequential development of steatosis (4-8 weeks), steatohepatitis with ballooning and Mallory-Denk bodies (12-16 weeks), progressive fibrosis (16 week onwards) and spontaneous HCC (32-52 weeks). The mice developed obesity, insulin resistance and dyslipidemia. There was concordance with the human NASH transcriptome (FDR 0.001) with activation of lipogenic, inflammatory and apoptotic pathways relevant in humans. The HCC gene signature resembled S1 and S2 human HCC subclass (FDR 0.01 for both). This simple model of NASH and HCC that resembles human disease in terms of its triggers, physiological and biochemical parameters, histology, transcriptomic profile, and outcomes can facilitate preclinical development for these conditions. 129S1/SvImJ;C57Bl/6J (129/B6) mice were fed with high-fat diet (Western Diet) and high fructose-glucose solution (Sugar Water) (WD SW) or chow diet (CD) for 8 weeks, and total RNA samples were isolated from liver tissues for genome-wide expression profiling.

2016-07-25 | E-GEOD-67678 | biostudies-arrayexpress

Effects of NAFLD/NASH on hepatic gene expression.

Project description:To characterize gene expression changes in arachidonic acid metabolism pathway genes in the presense of non-alcoholic fatty liver disease (NAFLD)/non-alcoholic steatohepatitis (NASH) mice administered were administered an atherogenic diet for a period of four weeks. Administration of the atherogenic diet resulted in significant enrichment of the arachidonic acid metabolism pathway by gene set enrichment analysis (GSEA). The core enrichment subset of genes was down-regulated in mice administered the atherogenic diet and the majority of the genes that were down-regulated were cytochrome P450s. A total of 4 wild-type mice were administered a standard diet (STD; control group) and 4 wild-type mice were administered a HFHC diet (HFHC).

2014-01-03 | E-GEOD-53381 | biostudies-arrayexpress

Gene expression profiles of livers and liver tumors from mice fed high-fat diet and high fructose-glucose solution for 52 weeks

2016-07-25 | GSE67679 | GEO

Gene expression profiles of livers from mice fed high-fat diet and high fructose-glucose solution for 8 weeks

2016-07-25 | GSE67678 | GEO

Sparcl1 promotes nonalcoholic steatohepatitis progression through upregulation of CCL2

Project description:1. White adipose tissues (WAT) are capable of secreting not only fatty acids but also a class of secretory proteins that modulate the homeostasis of distant organs, including the liver. To identify potential WAT-enriched secretory factors involved in NASH progression, C57BL/6 male mice were fed with a normal chow diet or HFHC diet for two different periods: 12 weeks and 28 weeks. Then, we compared the expression profile of epididymal WAT (eWAT) from mouse models of NAFL and NASH above mentioned by RNA-Sequencing analysis. 2. To investigate the contribution of Sparcl1 in the pathogenesis of NASH, male C57BL/6J mice were fed a HFHC diet for 12 weeks, and then intraperitoneal injected with saline or recombinant Sparcl1 protein (0.2mg/kg) every other day for 3 weeks. To elucidate the molecular basis of Sparcl1-mediated NASH progression, we conducted RNA-Sequencing analysis for differentially expressed genes using the livers of chronic recombinant Sparcl1 protein or saline- treated mice.

2021-06-10 | GSE176681 | GEO

Metabolomics and Lipidomics Screening Reveal Reprogrammed Signaling Pathways toward Cancer Development in Non-Alcoholic Steatohepatitis

Project description:Non-alcoholic fatty liver disease is now considered the most common form of chronic liver disease. It is a complex metabolic disease that silently progresses into non-alcoholic steatohepatitis (NASH). In fact, NASH is the tipping point for pericellular fibrosis, cirrhosis and hepatocellular carcinoma (HCC). Despite being a complex metabolic disease, identification of the metabolic readout that functions in metabolic pathway perpetuation for HCC progression from NASH is still incompletely understood. With the aid of LC MS/MS this study unveiled the metabolic fingerprint of NASH and HCC-NASH patients and it illustrates a detailed map for the most predominant reprogrammed metabolic pathways that target HCC development from NASH. https://doi.org/10.3390/ijms24010210

2021-08-19 | MSV000088003 | MassIVE

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

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