Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1103676 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR28778876_1.fastq.gz | Fastqsanger.gz | |||
| SRR28778876_2.fastq.gz | Fastqsanger.gz | |||
| SRR28778877_1.fastq.gz | Fastqsanger.gz | |||
| SRR28778877_2.fastq.gz | Fastqsanger.gz | |||
| SRR28778878_1.fastq.gz | Fastqsanger.gz |
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Project description:Alcoholic liver disease (ALD) encompasses conditions ranging from simple steatosis to cirrhosis and even liver cancer. It has gained significant global attention in recent years. Despite this, effective pharmacological treatments for ALD remain elusive, and the core mechanisms underlying the disease are not yet fully comprehended. S100A16, a newly identified calcium-binding protein, is linked to lipid metabolism. Our research has discovered elevated levels of the S100A16 protein in both serum and liver tissue of ALD patients. A similar surge in hepatic S100A16 expression was noted in a Gao-binge alcohol feeding mouse model. S100a16 knockdown alleviated ethanol-induced liver injury, steatosis and inflammation. Conversely, S100a16 transgenic mice showed aggravating phenomenon. Mechanistically, we identify mesencephalic astrocyte-derived neurotrophic factor (MANF) as a regulated entity downstream of S100a16 deletion. MANF inhibited ER-stress signal transduction induced by alcohol stimulation. Meanwhile, MANF silencing suppressed the inhibition effect of S100a16 knockout on ethanol-induced lipid droplets accumulation in primary hepatocytes. Our data suggested that S100a16 deletion protects mice against alcoholic liver lipid accumulation and inflammation dependent on upregulating MANF and inhibiting ER stress. This offers a potential therapeutic avenue for ALD treatment.
2023-09-26 | GSE243683 | GEO
Project description:Human Yes Associated Protein (hYAP) expressing mouse liver
| PRJNA384350 | ENA
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
Project description:Alcohol-associated liver disease is accompanied by changes in the intestinal mycobiome. How fungal dysbiosis contributes to liver disease is not clear. T-helper (Th17) cells mediate immune responses against fungi, but the interleukin 17 (IL17) pathway has been associated with pathogenesis of alcohol-associated liver disease. Here, we demonstrate that Candida albicans (C. albicans)-specific Th17 cells are increased in the circulation and present in the liver of patients with alcohol-associated liver disease. Chronic ethanol administration to mice results in migration of C. albicans-reactive Th17 cells from the intestine to the liver. The antifungal agent nystatin reduced intestinal fungal overgrowth, decreased C. albicans-specific Th17 cells in the liver, and reduced features of ethanol-induced liver disease in mice. Transgenic mice that express a T-cell receptor (TCR) reactive to Candida antigens develop more severe ethanol-induced liver disease than transgene-negative littermates; disease severity was reduced by administration of an antibody against IL17 to the TCR transgenic mice. Adoptive transfer of C. albicans-reactive Th17 cells exacerbated ethanol-induced liver disease in wild-type mice. IL17 receptor A (IL17ra) signaling in Kupffer cells was required for the effects of C. albicans-reactive Th17 cells. Our findings indicate that ethanol increases C. albicans-reactive Th17 cells, which contribute to alcohol-associated liver disease.
2023-02-16 | GSE215929 | GEO
Project description:Alcohol-associated liver disease is accompanied by changes in the intestinal mycobiome. How fungal dysbiosis contributes to liver disease is not clear. T-helper (Th17) cells mediate immune responses against fungi, but the interleukin 17 (IL17) pathway has been associated with pathogenesis of alcohol-associated liver disease. Here, we demonstrate that Candida albicans (C. albicans)-specific Th17 cells are increased in the circulation and present in the liver of patients with alcohol-associated liver disease. Chronic ethanol administration to mice results in migration of C. albicans-reactive Th17 cells from the intestine to the liver. The antifungal agent nystatin reduced intestinal fungal overgrowth, decreased C. albicans-specific Th17 cells in the liver, and reduced features of ethanol-induced liver disease in mice. Transgenic mice that express a T-cell receptor (TCR) reactive to Candida antigens develop more severe ethanol-induced liver disease than transgene-negative littermates; disease severity was reduced by administration of an antibody against IL17 to the TCR transgenic mice. Adoptive transfer of C. albicans-reactive Th17 cells exacerbated ethanol-induced liver disease in wild-type mice. IL17 receptor A (IL17ra) signaling in Kupffer cells was required for the effects of C. albicans-reactive Th17 cells. Our findings indicate that ethanol increases C. albicans-reactive Th17 cells, which contribute to alcohol-associated liver disease.
2023-02-16 | GSE215930 | GEO
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
Project description:Human Yes Associated Protein (hYAP) expressing mouse liver (set 2)
| PRJNA384356 | ENA
Project description:Human Yes Associated Protein (hYAP) expressing mouse liver (set 1)
| PRJNA384357 | ENA
Project description:Scope: Alcoholic liver disease (ALD) is a major cause of chronic liver disease and is induced by alcohol consumption. Acetaldehyde produced by alcohol metabolism enhances the fibrosis of the liver through hepatic stellate cells. Additionally, alcohol administration causes the accumulation of reactive oxygen species (ROS), which induce hepatocyte-injury-mediated lipid peroxidation. The purpose of this study was to investigate the protective effects of iso-α-acids against alcoholic liver injury in hepatocytes in mice. Methods and results: C57BL/6N mice were fed diets containing isomerized hop extract, which mainly consists of iso-α-acids. After 7 days of feeding, acetaldehyde was administered by a single intraperitoneal injection. The acetaldehyde-induced increases in serum AST and ALT levels were suppressed by iso-α-acids intake. Hepatic gene expression analyses showed the upregulation of the glutathione-S-transferase, alcohol dehydrogenase and aldehyde dehydrogenase genes. In vitro, iso-α-acids induced the nuclear translocation of nuclear factor erythroid 2-like 2 (Nfe2l2; Nrf2), a master regulator of antioxidant and detoxifying systems, and upregulated the enzymatic activities of glutathione-S-transferase and aldehyde dehydrogenase. Conclusions: These results suggest that iso-α-acids intake prevents alcoholic liver disease injury by reducing oxidative stress via the Nrf2-mediated pathway.
2021-02-10 | GSE140387 | GEO
Project description:Background: Alcohol-associated hepatitis (AH) is the clinical manifestation of alcohol-associated liver disease (ALD). AH is a complex disease encompassing the dysregulation of many cells and cell subpopulations. This study used a hepatic spatial transcriptomic and proteomic approach (10X Genomics Visium) to identify hepatic cell populations and their associated transcriptomic and proteomic alterations in human AH. Methods: Formalin fixed parraffin embedded liver tissue from AH patients (n=2) and non-ALD controls (donors) (n=2) were used for Visium spatial transcriptomic and proteomic analysis. Results: AH cell clusters and cell markers were drastically different in regard to tissue pattern and number of cell type as compared to non-ALD controls. Cholangiocytes, endothelial cells, macrophages, and stellate cells were more profuse in AH relative to non-ALD controls. Transcriptionally, proliferating cell nuclear antigen positive (PCNA+) hepatocytes in AH more closely resembled cholangiocytes suggesting they were non-functional hepatocytes derived from cholangiocytes. Further, mitochondria protein coding genes were reduced in AH vs non-ALD control hepatocytes, suggesting reduced functionality and loss of regenerative mechanisms. Macrophages in AH exhibited elevated gene expression involved in exosomes as compared to non-ALD controls. The most upregulated macrophage genes observed in AH were those involved in exosome trafficking and cellular migration. Gene and protein signatures of disease associated hepatocytes (ANXA2+/CXCL1+/CEACAM8+) were elevated in AH and could visually identify a pre-malignant lesion. Conclusions: This study identified global cell type alterations in AH and distinct transcriptomic changes between AH and non-ALD controls. These findings characterizes cellular plasticity and profuse transcriptomic and proteomic changes that are apparent in AH and contributes to the identification of novel therapeutics.
2024-12-02 | GSE278662 | GEO