Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Investigating multigenerational epigenetic adaptation of the hepatic wound-healing response

ABSTRACT: The possibility that ancestral environmental conditions and exposures could result in effects inherited across generations, with potential impact for human health, has been long debated. Here, we comprehensively investigate transgenerational effects of the hepatotoxicant carbon tetrachloride (CCl4) on the hepatic wound-healing response in male rats. Detailed microscopic and clinical pathology evaluations do not support adaptive phenotypic suppression of the hepatic wound-healing response or a greater fitness of animals with ancestral liver injury exposure as originally reported. We produced RNAseq libraries on the F2 liver samples to further characterize any adaptive effect based on molecular changes.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE229524 | GEO | 2023/09/06

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Investigating multigenerational epigenetic adaptation of the hepatic wound-healing response

Project description:Investigating multigenerational epigenetic adaptation of the hepatic wound-healing response

| PRJNA954835 | ENA

Metabolic Reprogramming and Reliance in Human Skin Wound Healing

Project description:Impaired skin wound healing is a significant global health issue, especially among the elderly. Wound healing is a well-orchestrated process involving the sequential phases of inflammation, proliferation, and tissue remodeling. Although wound healing is a highly dynamic and energy-requiring process, the role of metabolism remains largely unexplored. By combining transcriptomics and metabolomics of human skin biopsy samples, we mapped the core bioenergetic and metabolic changes in normal acute as well as chronic wounds in elderly subjects. We found upregulation of glycolysis, the tricarboxylic acid cycle, glutaminolysis, and β-oxidation in the later stages of acute wound healing and in chronic wounds. To ascertain the role of these metabolic pathways on wound healing, we targeted each pathway in a wound healing assay as well as in a human skin explant model using metabolic inhibitors and stimulants. Enhancement or inhibition of glycolysis and, to a lesser extent, glutaminolysis had a far greater impact on wound healing than similar manipulations of oxidative phosphorylation and fatty acid β-oxidation. These findings increase the understanding of wound metabolism and identify glycolysis and glutaminolysis as potential targets for therapeutic intervention.

2024-07-02 | MTBLS3315 | MetaboLights

Gene expression profiles of rat liver tissues after carbon tetrachloride treatment

Project description:Acute hepatic failure (AHF) usually occurs due to the rapid necrosis of liver cells or serious liver injury induced by a variety of pathogenic factors. We used Rat Genome 230 2.0 microarray to further highlight the rat liver tissues after carbon tetrachloride treatment.

2015-09-29 | GSE73494 | GEO

Gene expression profiles of rat liver tissues after carbon tetrachloride administration

Project description:Liver cirrhosis (LC) is pathologically characterized with abnormality and necrosis of hepatic cells, proliferation of fibrous tissue, nodular regeneration and pseudolobule formation. We used Rat Genome 230 2.0 microarray to further highlight the rat liver tissues after carbon tetrachloride administration

2015-09-29 | GSE73499 | GEO

DNMT3a-mediated methylation of TCF21/hnRNPA1 aggravates liver fibrosis by regulating the NF-κB signaling pathway

Project description:Hepatic fibrosis is caused by liver damage as a consequence of wound healing response. Recent studies have shown that hepatic fibrosis could be effectively reversed, partly through regression of activated hepatic stellate cells (HSCs). Transcription factor 21 (TCF21), a member of the basic helix-loop-helix (bHLH) transcription factor, is involved in epithelial-mesenchymal transformation in various diseases. However, the mechanism by which TCF21 regulates epithelial-mesenchymal transformation in hepatic fibrosis has not been elucidated. In this research, we found that hnRNPA1, the downstream binding protein of TCF21, accelerates liver fibrosis reversal by inhibiting the NF-κB signaling pathway. Furthermore, the combination of DNMT3a with TCF21 promoter results in TCF21 hypermethylation. Our results suggest that DNMT3a regulation of TCF21 is a significant event in reversing hepatic fibrosis. In conclusion, this research identifies a novel signaling axis, DNMT3a-TCF21-hnRNPA1, that regulates HSCs activation and liver fibrosis reversal, providing a novel treatment strategy for hepatic fibrosis.

2024-10-01 | GSE232674 | GEO

Discover preclinical biomarkers of hepatotoxicity: Acetaminophen and Carbon tetrachloride

Project description:Preclinical biomarkers useful for identification of idiosyncratic drugs have not been identified. It is hypothesized that patterns of transcript expression for the hepatotoxicants, including classical and idiosyncratic hepatotoxicants, are similar and the patterns differ from those of non-hepatotoxicants. This experiment is part of the biomarkers study, and focus on two clasical hepatotoxicants: Acetaminophen and Carbon tetrachloride. We have employed whole genome microarray expression profiling to identify liver gene expression changes induced by hepatotoxicants. For the same animal, urinary microRNA profiling were analyzed. APAP and CCl4 both significantly increased the urinary levels of 44 and 28 miRNAs, respectively. In addition, 10 of the increased miRNAs were in common between APAP and CCl4. Computational analysis was used to predict target genes of the 10 shared hepatotoxicant-induced miRNAs. From the same animals, liver gene expression profiling was performed using whole genome microarrays. Eight putative target genes were found to be significantly altered in the liver of APAP and CCl4 treated animals. Acetaminophen induced liver gene expression changes in rats (Six to seven week-old male Sprague-Dawley rats, provided by the US Food and Drug Administration National Center for Toxicological Research (NCTR) breeding colonies, were used for the study.) were measured at 6 hours, 24 hours, 3 days and 7 days after exposure to doses of 0, 100 and 1250 mg/kg. Carbon tetrachloride induced liver gene expression changes in rats were measured at 6 hours, 24 hours and 3 days after exposure to doses of 0, 50 and 2000 mg/kg. Each group has at least 4 animals, total of 96 samples.

2012-03-15 | E-GEOD-32891 | biostudies-arrayexpress

E-MTAB-9864

Project description:INSIG1 in NASH pathophysiology and in the hepatic wound-healing response

2020-12-11 | E-MTAB-9864 | ExpressionAtlas

Follistatin-like 1 guarantees the immunomodulatory properties of mesenchymal stem cells during liver fibrotic therapy

Project description:Mesenchymal stem cell (MSC) therapy has been shown to be a promising option for liver fibrosis treatment. However, critical factors affecting the efficacy of MSC therapy for liver fibrosis remain unknown. Follistatin-like 1 (FSTL1), a TGF--induced matricellular protein, is documented as an intrinsic regulator of proliferation and differentiation in MSCs. In the present study, we characterized the potential role of FSTL1 in MSC-based anti-fibrotic therapy and further elucidated the mechanisms underlying its action. Human umbilical cord-derived MSCs were characterized by flow cytometry. FSTL1low MSCs was achieved by FSTL1 siRNA. Migration capacity was evaluated by wound-healing and transwell assay. A murine liver fibrotic model was created by carbon tetrachloride (CCl4) injection, while control MSCs or FSTL1low MSC were transplanted via intravenous injection 12 weeks post CCl4 injection. Histopathology, liver function, fibrosis degree, and inflammation were analysed thereafter. Inflammatory cell infiltration was evaluated by flow cytometry after hepatic nonparenchymal cell isolation. An MSC-macrophage co-culture system was constructed to further confirm the role of FSTL1 in the immunosuppressive capacity of MSCs. RNA sequencing was used to screen target genes of FSTL1. FSTL1low MSCs had comparable gene expression for surface markers to wildtype but limited differentiation and migration capacity. FSTL1low MSCs failed to alleviate CCl4-induced hepatic fibrosis in a mouse model. Our data indicated that FSTL1 is essential for the immunosuppressive action of MSCs on inflammatory macrophages during liver fibrotic therapy. FSTL1 silencing attenuated this capacity by inhibiting the downstream JAK/STAT1/IDO pathway. Our data suggest that FSTL1 facilitates the immunosuppression of MSCs on macrophages and that guarantee the anti-fibrotic effect of MSCs in liver fibrosis.

2024-04-30 | GSE202320 | GEO

Enhancing wound inducible adaptive fibroblast reprogramming overcomes diabetic healing impairment

Project description:Enhancing wound inducible adaptive fibroblast reprogramming overcomes diabetic healing impairment

| PRJNA704577 | ENA

In vitro activation and reversion of human primary hepatic stellate cells

Project description:Liver fibrosis is characterized by the excessive formation and accumulation of matrix proteins as a result of wound healing in the liver. A main event during fibrogenesis is the activation of the liver resident quiescent hepatic stellate cell (qHSC). Recent studies suggest that reversion of the activated HSC (aHSC) phenotype into a quiescent-like phenotype could be a major cellular mechanism underlying fibrosis regression in the liver, thereby offering new therapeutic perspectives for the treatment of liver fibrosis. The goal of the present study is to identify experimental conditions that can revert the activated status of human HSCs and to map the molecular events associated with this phenotype reversion by gene expression profiling Transcriptomic profiling of primary human quiescent HSCs (qHSCs), in vitro activated HSCs (aHSCs) and in vitro reverted HSCs (rHSCs). The cell types come from different donors (This is detailed in the original manuscript.).

2015-08-12 | E-GEOD-68001 | biostudies-arrayexpress

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