Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Human Beta Defensin 2 Ameliorated Alcohol-Associated Liver Disease in Mice

ABSTRACT: Human Beta Defensin 2 in Alcohol-Associated Liver Disease

PROVIDER: PRJEB49248 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	ERR7681520.fastq.gz	Fastqsanger.gz
	ERR7681530.fastq.gz	Fastqsanger.gz
	ERR7681540.fastq.gz	Fastqsanger.gz
	ERR7681550.fastq.gz	Fastqsanger.gz
	ERR7681560.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 118

Similar Datasets

Human Beta Defensin 2 Ameliorated Alcohol-Associated Liver Disease in Mice.

Project description:Alcohol-associated liver disease (ALD) is a prevalent liver disorder and significant global healthcare burden with limited effective therapeutic options. The gut-liver axis is a critical factor contributing to susceptibility to liver injury due to alcohol consumption. In the current study, we tested whether human beta defensin-2 (hBD-2), a small anti-microbial peptide, attenuates experimental chronic ALD. Male C57Bl/6J mice were fed an ethanol (EtOH)-containing diet for 6 weeks with daily administration of hBD-2 (1.2 mg/kg) by oral gavage during the final week. Two independent cohorts of mice with distinct baseline gut microbiota were used. Oral hBD-2 administration attenuated liver injury in both cohorts as determined by decreased plasma ALT activity. Notably, the degree of hBD-2-mediated reduction of EtOH-associated liver steatosis, hepatocellular death, and inflammation was different between cohorts, suggesting microbiota-specific mechanisms underlying the beneficial effects of hBD-2. Indeed, we observed differential mechanisms of hBD-2 between cohorts, which included an induction of hepatic and small intestinal IL-17A and IL-22, as well as an increase in T regulatory cell abundance in the gut and mesenteric lymph nodes. Lastly, hBD-2 modulated the gut microbiota composition in EtOH-fed mice in both cohorts, with significant decreases in multiple genera including Barnesiella, Parabacteroides, Akkermansia, and Alistipes, as well as altered abundance of several bacteria within the family Ruminococcaceae. Collectively, our results demonstrated a protective effect of hBD-2 in experimental ALD associated with immunomodulation and microbiota alteration. These data suggest that while the beneficial effects of hBD-2 on liver injury are uniform, the specific mechanisms of action are associated with baseline microbiota.

| S-EPMC8829467 | biostudies-literature

Effect of human beta defensin-2 (hBD-2) on T cells [mouse]

Project description:In this experiment, we studied how human beta defensin-2 (hBD-2) affects kinase activity of T cells.

2022-12-20 | GSE198404 | GEO

Effect of human beta defensin-2 (hBD-2) on T cells [human]

Project description:In this experiment, we studied how human beta defensin-2 (hBD-2) affects kinase activity of T cells.

2022-12-20 | GSE198402 | GEO

Effect of human beta defensin-2 (hBD-2) on T cells

Project description:In this experiment, we studied how human beta defensin-2 (hBD-2) affects gene expression of T cells. Murine splenic C57BL/6 CD4/CD8 T cells were stimulated with anti-CD3/anti-CD28 beads and hBD-2 or vehicle (PBS) control for 48h before RNA isolation

2022-12-23 | GSE190797 | GEO

Sex specific role of KDM5 demethylases in Alcohol-associated Liver Disease

Project description:Alcohol-associated liver disease (ALD) is a major cause of alcohol related mortality. The specific mechanisms responsible for ALD development and progression are not fully understood, and there is limited therapy for any stage of ALD. Sex differences are often disregarded in in genetic and mechanistic studies. We aimed to take an unbiased approach to define sex specific pathways in livers exposed to alcohol. METHODS: Mice were fed LieberDeCarli alcohol liquid diet for 3 weeks. To identify the role of Kdm5b and Kdm5c we injected mice with AAV-shControl at 2x10^11 gc per mouse or AAV-shKdm5b and AAV-Kdm5c vectors at 10^11 gc per mouse. To assess the role of AhR we injected mice with AAV-shControl or AAV-shAhR vectors at 10^11 gc per mouse. RESULTS: We found several pathways affected by alcohol in sex specific way and identified KDM5 demethylases as contributors to that specificity.

2022-02-08 | GSE195889 | GEO

The role of Cebpb in Alcohol-associated Liver Disease development and resolution

Project description:Abstinence is an important therapeutic intervention for patients with alcohol-associated liver disease (ALD). However, fibrosis improvement after cessation is not uniform and some patients do not improve. We aimed to use scATAC-seq analysis in a mouse model of ALD to define the mechanism of poor ALD resolution. We analyzed differentially accessible regions in livers from control, ALD, or 4 weeks post alcohol cessation mice and identified transcription factors activated in ALD that remained activated after alcohol withdrawal. The top hit was C/EBPβ. We found that hepatocyte specific Cebpb knockout prevented ALD development, while knockout at the time of alcohol cessation promoted fibrosis resolution.

2024-09-12 | GSE276692 | GEO

Depletion of Mitochondrial Methionine Adenosyltransferase α1 Triggers Mitochondrial Dysfunction in Alcohol-Associated Liver Disease

Project description:Mitochondrial MATα1 is selectively depleted in alcohol-associated liver disease through a mechanism that involves the isomerase PIN1 and the kinase CK2. Alcohol activates CK2, which phosphorylates MATα1 at Ser114 facilitating interaction with PIN1, thereby inhibiting its mitochondrial localization. Blocking PIN1-MATα1 interaction increased mitochondrial MATα1 levels and protected against alcohol-induced mitochondrial dysfunction.

2022-02-17 | PXD030383 | Pride

Sex specific role of KDM5B demethylase in Alcohol-associated Liver Disease development and resolution

Project description:Alcohol-associated liver disease (ALD) is a major cause of alcohol related mortality. Recently we identified hepatic demethylases KDM5B and KDM5C as important sex-specific epigenetic regulators of alcohol response in the liver. In this study we aimed to study the molecular mechanisms of KDM5-dependent ALD development and resolution. We found that alcohol induces pathological changes in cell-cell communication in the liver that are in part mediated by epigenetic changes in hepatocytes mediated by histone demethylase KDM5B. Using cell type specific knockout mice, we found that KDM5B histone demethylase was a key regulator of alcohol-induced epigenetic changes in hepatocytes. Moreover, it regulated hepatocytes-non-parenchymal cell crosstalk that promoted inflammation and fibrosis development in ALD. This mechanism was specific to females. In males KDM5B deficiency was not sufficient to prevent fibrosis development. In contrast KDM5B demethylase loss promoted fibrosis resolution in both males and females. This mechanism involved changes in hepatocyte-macrophage crosstalk and LXRα activation, which we identified to be critical for the fibrosis resolution process. CONCLUSION: In summary, KDM5B demethylase is a regulator of cell-cell crosstalk involved in disease progression in females and in disease resolution in both sexes.

2023-10-07 | GSE244240 | GEO

Transcriptomics of liver and PBMCs in alcohol-associated liver disease

Project description:Transcriptomics of liver and PBMCs in alcohol-associated liver disease

| PRJNA899977 | ENA

Transcriptomics of liver and PBMCs in alcohol-associated liver disease

Project description:Transcriptomics of liver and PBMCs in alcohol-associated liver disease

| PRJNA899978 | ENA