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A regulatory loop involving the cytochrome P450-soluble epoxide hydrolase axis and TGF-b signaling

ABSTRACT: A regulatory loop involving the cytochrome P450-soluble epoxide hydrolase axis and TGF-b signaling

PROVIDER: PRJNA1143571 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR30117039.fastq.gz	Fastqsanger.gz
	SRR30117040.fastq.gz	Fastqsanger.gz
	SRR30117041.fastq.gz	Fastqsanger.gz
	SRR30117042.fastq.gz	Fastqsanger.gz
	SRR30117043.fastq.gz	Fastqsanger.gz

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Similar Datasets

A regulatory loop involving the cytochrome P450-soluble epoxide hydrolase axis and TGF-b signaling

Project description:Fatty acid metabolites generated by the sequential actions of cytochrome P450 enzymes and the soluble epoxide hydrolase (sEH) regulate inflammation. Here we report that the TGF--induced polarization of macrophages to a pro-resolving phenotype requires the activation of Alk5 and Smad2 to increase sEH expression and activity. Macrophages lacking sEH failed to fully repolarize, were less efficient at phagocytosis, and retained a pro-inflammatory gene expression profile. 11,12-Epoxyeicosatrienoic acid (EET) was one of the fatty acid metabolites altered in sEH-/- macrophages and was able to reproduce the effect of sEH deletion on gene expression. Importantly, 11,12-EET also attenuated the expression of Alk5 to inhibit the TGF--induced phosphorylation of Smad2 by eliciting the cytosolic translocation of the E3 ligase Smurf2. These results indicate that the expression of sEH is not only controlled by TGF- but that the activity of the enzyme, which keeps 11,12-EET levels low, actually promotes TGF- signaling by preventing the proteolytic degradation of Alk5. Thus, an autocrine loop between the sEH/11,12-EET and TGF-1 determines macrophage function.

2024-08-15 | GSE273900 | GEO

Characterization of genome-modified Caenorhabditis elegans expressing the human cytochrome P450 (CYP1A1 and CYP1A2) pathway

Project description:Polycyclic aromatic hydrocarbons (PAHs), such as benzo[a]pyrene (BaP), are produced by the incomplete combustion of organic matter and thus are present in tobacco smoke, charbroiled food and diesel exhaust. The nematode Caenorhabditis elegans lacks the genetic components of the classical mammalian cytochrome P450 (CYP)-mediated BaP-diol-epoxide metabolism pathway thus CYP1A1 or CYP1A2 together with human epoxide hydrolase (EPHX) was introduced into the worm genome, thereby allowing to study potential physiological, genomic and transcriptional changes after BaP exposure in these CYP-humanised C. elegans strains. Strain and exposure specific changes in the transcriptome were identified by means of RNAseq. thereby demonstrating the amenity of introducing human genes into the C. elegans genome and their utility to serve as a model for environmental carcinogenesis and pharmacological research.

2025-06-24 | GSE271716 | GEO

Mutational signatures of genome-modified Caenorhabditis elegans expressing the human cytochrome P450 (CYP1A1 and CYP1A2) pathway

Project description:Polycyclic aromatic hydrocarbons (PAHs), such as benzo[a]pyrene (BaP), are produced by the incomplete combustion of organic matter and thus are present in tobacco smoke, charbroiled food and diesel exhaust. The nematode Caenorhabditis elegans lacks the genetic components of the classical mammalian cytochrome P450 (CYP)-mediated BaP-diol-epoxide metabolism pathway thus CYP1A1 or CYP1A2 together with human epoxide hydrolase (EPHX) was introduced into the worm genome, thereby allowing to study potential physiological, genomic and transcriptional changes after BaP exposure in these CYP-humanised C. elegans strains. Whole genome sequencing revealed a higher frequency of T>G base substitution mutations in worms expressing human CYP1A1;EPHX thereby demonstrating the amenity of introducing human genes into the C. elegans genome and their utility to serve as a model for environmental carcinogenesis and pharmacological research.

2025-06-24 | GSE272108 | GEO

Soluble epoxide hydrolase inhibition confers neuroprotective and anti-inflammatory effect in a tauopathy mouse model

Project description:Inhibition of soluble epoxide hydrolase (sEH) has been shown to suppress neuroinflammation through stabilizing epoxy fatty acids. Here we examined the role of sEH inhibitor TPPU in PS19 tauopathy mouse model by treating the 6-month-old wild-type and PS19 mice with vehicle or TPPU via drinking water continuously for 12 weeks, followed by performing single nucleus RNA-sequencing of the hippocampal tissues of the treated mice.

2025-04-30 | GSE272373 | GEO

A regulatory loop involving the cytochrome P450-soluble epoxide hydrolase axis and TGF-β signaling.

Project description:Fatty acid metabolites, produced by cytochrome P450 enzymes and soluble epoxide hydrolase (sEH), regulate inflammation. Here, we report that the transforming growth factor β (TGF-β)-induced polarization of macrophages to a pro-resolving phenotype requires Alk5 and Smad2 activation to increase sEH expression and activity. Macrophages lacking sEH showed impaired repolarization, reduced phagocytosis, and maintained a pro-inflammatory gene expression profile. 11,12-Epoxyeicosatrienoic acid (EET) was one altered metabolite in sEH-/- macrophages and mimicked the effect of sEH deletion on gene expression. Notably, 11,12-EET also reduced Alk5 expression, inhibiting TGF-β-induced Smad2 phosphorylation by triggering the cytosolic translocation of the E3 ligase Smurf2. These findings suggest that sEH expression is controlled by TGF-β and that sEH activity, which lowers 11,12-EET levels and promotes TGF-β signaling by metabolizing 11,12-EET to prevent Alk5 degradation. Thus, an autocrine loop between sEH/11,12-EET and TGF-β1 regulates macrophage function.

| S-EPMC11466655 | biostudies-literature

Identification and developmental expression of the full complement of cytochrome P450 genes in zebrafish

Project description:To determine the expression of cytochrome P450 genes during normal development

2010-10-21 | GSE24840 | GEO

Soluble Epoxide Hydrolase Inhibition Attenuated Chronic Alcohol-Associated Liver Injury and Altered the Hepatic Proteome in Mice

Project description:Effect of soluble epoxide hydrolase inhibition on alcohol-associated liver disease

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The Role of Cytochrome P450 Epoxygenases, Soluble Epoxide Hydrolase, and Epoxyeicosatrienoic Acids in Metabolic Diseases.

Project description:Metabolic diseases are associated with an increased risk of developing cardiovascular disease. The features comprising metabolic diseases include obesity, insulin resistance, hyperglycemia, hyperlipidemia, and hypertension. Recent evidence has emerged showcasing a role for cytochrome P450 epoxygenases, soluble epoxide hydrolase, and epoxyeicosatrienoic acids (EETs) in the development and progression of metabolic diseases. This review discusses the current knowledge related to the modulation of cytochrome P450 epoxygenases and soluble epoxide hydrolase to alter concentrations of biologically active EETs, resulting in effects on insulin resistance, lipid metabolism, obesity, and diabetes. Future areas of research to address current deficiencies in the understanding of these enzymes and their eicosanoid metabolites in various aspects of metabolic diseases are also discussed.

| S-EPMC5105036 | biostudies-literature

Inhibition of Soluble Epoxide Hydrolase is Protective Against the Multiomic Effects of a High Glycemic Diet on Brain Microvascular Inflammation and Cognitive Dysfunction

Project description:Diet is a modifiable risk factor for cardiovascular disease (CVD) and dementia, yet relatively little is known about the effect of a high glycemic diet (HGD) on the brain microvasculature. The objective of our study was to determine the molecular effects of a HGD on hippocampal microvessels and cognitive function, and to determine if a soluble epoxide hydrolase (sEH) inhibitor (sEHI), known to be vasculoprotective and anti-inflammatory, modulates these effects. Global hippocampal microvascular gene expression was fundamentally different for mice fed the HGD vs the LGD. The HGD response was characterized by differential expression of 608 genes involved in cell signaling, neurodegeneration, metabolism, and cell adhesion/inflammation/oxidation effects reversible by t-AUCB and hence sEH inhibitor correlated with protection against Alzheimer’s dementia.

2021-12-07 | GSE185057 | GEO

Differential Multigenomic Effect of Soluble Epoxide Hydrolase Inhibition on the Hippocampal Brain Microvasculature of FeFemale Mice on Low and High Glycemic Diets.

Project description:Microvascular dysfunction is central to the development of dementia. The effect of high glycemic diet (HGD), independent from dietary fat, on brain microvasculature is crucial, yet an understudied research topic, especially in feFemales. Our study aimed to determine the transcriptomic changes in feFemale brain hippocampal microvasculature induced by a HGD and characterize the response to soluble epoxide hydrolase inhibitor (sEHI). We demonstrated for the first time in feFemales that the HGD had an opposite gene expression profile compared to the LGD and differentially expressed 506 genes, primarily downregulated, with functions related to cell signaling, cell adhesion, cellular metabolism, and neurodegenerative diseases. Surprisingly, the sEHI modified the transcriptome of feFemale mice consuming the LGD more than the HGD, by modulating genes involved in metabolic pathways that synthesize neuroprotective epoxyeicosatrienoic acids (EETs) and associated with a higher EETs/ dihydroxyeicosatrienoic acids (DHETs) ratio.

2022-11-16 | GSE195975 | GEO

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