Single-cell transcriptome characterization of the livers from patients with alcoholic liver disease
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE236382 | GEO | 2023/07/03
REPOSITORIES: GEO
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Project description:Alcoholic liver disease (ALD) is a kind serious liver disease, which will develope into the cirrhosis, liver cancer and so on. The study results show that riboflavin has the protective effect against ALD. Then the study divides the C57BL/6 mice into the three groups that were Control (C), Alcohol, Alcohol with riboflavin (AR) groups respectively. And the study makes the mouse liver RNA sequencing (RNA-seq) to find the differential expression mRNAs among three groups futher and does the related analysis in riboflavin-treated alcoholic liver disease.
2024-08-28 | GSE273208 | GEO
Project description:Alcoholic liver disease (ALD) is a kind of liver disease that will result in liver cancer and some other high death rate liver disease. The study results show that riboflavin could protect the mouse against ALD. Then the study divides the C57BL/6 mice into the three groups including Control (C), Alcohol, Alcohol with riboflavin (AR) groups respectively. And the study makes the mouse stool samples 16S RNA sequencing (RNA-seq) to find the differential itestinal microbiota homeostasis among three groups futher and does the related analysis in riboflavin-treated alcoholic liver disease.
2024-08-28 | GSE273370 | GEO
Project description:Background and Aim: The worldwide prevalence of alcoholic liver disease (ALD) due to escalating alcohol consumption has presented an unprecedented pressure on human health. A few studies have determined long non-coding RNAs (lncRNAs) involved in the pathogenesis of liver diseases. However, the roles of lncRNAs in ALD development is still poorly understood. Methods: An ALD mouse model was established and confirmed. Expression profiles of lncRNAs were obtained by whole transcriptome sequencing. The altered lncRNAs in ALD mice were further verified by qRT-PCR. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were used to enrich the functions of these lncRNAs. In combination with miRNA and mRNA profiles, we constructed concise endogenous RNA (ceRNA) networks. The function of the most up/downregulated lnRNA signaling was further verified and investigated in both ALD model and AML-12 cells. Results: Totally, five downregulated lncRNAs were obtained and verified in ALD mice. The GO term and KEGG pathway analyses revealed that the identified lncRNAs were associated with alcohol-induced hepatic oxidative damage, cellular inflammation, and lipid metabolism. Integration the differentially modulated miRNAs and mRNAs with ceRNA network analysis, we constructed five ceRNA networks and screened out 30 miRNAs and 25 mRNAs that may participate in ALD. Further, we verified and investigate the function of the most downregulated lnc_1700023H06Rik. Depletion lnc_1700023H06Rik reduced genes related to lipid metabolism, especially mRNA Acat2 (ENSMUST00000159697) and Pgrmc2 (ENSMUST00000058578) in both ALD mice and AML12 cell. Knocking down lnc_1700023H06Rik induced triglyceride accumulation and LDH leakage in AML12 cells, consisting with that in alcohol-treated cells, confirming the potential pathological role of lnc_1700023H06Rik in ALD. Conclusion: The five remarkably downregulated lncRNAs in an ALD mouse model were identified as novel biomarkers, highlighting the key role of lncRNAs in the development of ALD. The effect of lnc_1700023H06Rik was further verified.
2021-08-18 | GSE175804 | GEO
Project description:Background and Aim: The worldwide prevalence of alcoholic liver disease (ALD) due to escalating alcohol consumption has presented an unprecedented pressure on human health. A few studies have determined long non-coding RNAs (lncRNAs) involved in the pathogenesis of liver diseases. However, the roles of lncRNAs in ALD development is still poorly understood. Methods: An ALD mouse model was established and confirmed. Expression profiles of lncRNAs were obtained by whole transcriptome sequencing. The altered lncRNAs in ALD mice were further verified by qRT-PCR. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were used to enrich the functions of these lncRNAs. In combination with miRNA and mRNA profiles, we constructed concise endogenous RNA (ceRNA) networks. The function of the most up/downregulated lnRNA signaling was further verified and investigated in both ALD model and AML-12 cells. Results: Totally, five downregulated lncRNAs were obtained and verified in ALD mice. The GO term and KEGG pathway analyses revealed that the identified lncRNAs were associated with alcohol-induced hepatic oxidative damage, cellular inflammation, and lipid metabolism. Integration the differentially modulated miRNAs and mRNAs with ceRNA network analysis, we constructed five ceRNA networks and screened out 30 miRNAs and 25 mRNAs that may participate in ALD. Further, we verified and investigate the function of the most downregulated lnc_1700023H06Rik. Depletion lnc_1700023H06Rik reduced genes related to lipid metabolism, especially mRNA Acat2 (ENSMUST00000159697) and Pgrmc2 (ENSMUST00000058578) in both ALD mice and AML12 cell. Knocking down lnc_1700023H06Rik induced triglyceride accumulation and LDH leakage in AML12 cells, consisting with that in alcohol-treated cells, confirming the potential pathological role of lnc_1700023H06Rik in ALD. Conclusion: The five remarkably downregulated lncRNAs in an ALD mouse model were identified as novel biomarkers, highlighting the key role of lncRNAs in the development of ALD. The effect of lnc_1700023H06Rik was further verified.
2021-08-18 | GSE179648 | GEO
Project description:Alcoholic liver disease (ALD) is one of the most prevalent types of liver disease associated with high morbidity and mortality, caused by hepatotoxicity originating from alcohol metabolism, but current therapeutic drugs are still limited. The role of ACSS2 as an enzyme that metabolizes acetate in ALD remains unknown. Our study aimed to investigate the function of ACSS2 and its potential mechanism in ALD progression.
2024-08-28 | GSE267638 | GEO
Project description:Ca2+ overload-induced mitochondrial dysfunction is considered as a major contributing factor in the pathogenesis of alcohol-associated liver disease (ALD). However, the initiating factors that drive mitochondrial Ca2+ accumulation in ALD remain elusive. Here, we demonstrate that an aberrant increase in mitochondria-associated ER membranes (MAMs) mediates Ca2+ accumulation-induced mitochondrial dysfunction in ALD via the formation of glucose-regulated protein 75 (GRP75)-mediated MAM Ca2+-channeling (MCC) complex. Unbiased transcriptomic analysis reveals pyruvate dehydrogenase kinase 4 (PDK4) as a prominently inducible MAM kinase in ALD. Additional mass spectrometry analysis unveils the critical role of PDK4 in promoting alcohol-induced MCC complex formation and mitochondrial dysfunction by phosphorylating GRP75. Non-phosphorylatable GRP75 mutation or genetic ablation of PDK4 prevents alcohol-induced mitochondrial Ca2+ accumulation and dysfunction. Conversely, ectopic induction of MAM formation in PDK4-deficient mice abrogate the protective effect in alcohol-induced liver injury. Together, our study defines the mediatory role of PDK4 in promoting mitochondrial dysfunction in ALD.
2023-05-10 | PXD039478 | Pride
Project description:Background and Aims: Lysophosphatidylcholine acyltransferase 3 (LPCAT3), a key molecule regulating intracellular phospholoesters has abundantly expression level in metabolic tissues including liver, intestine and adipose. And it is considered to be directly related to the biosynthesis of inflammatory lipid mediators in humans. However, the mechanism of LPCAT3 in alcoholic liver disease (ALD) is unclear. Approach and Results: Liver-specific LPCAT3 liver knockout (LPCAT3-LKO) mice were established using CRISPR/Cas9, and then an ALD model followed by NIAAA modele was established. After LPCAT3-specific knockout of liver tissue, ALT, AST, TG, TC and liver TG, TC in ALD mice were reduced. Our group found that three downstream targets of LPCAT3, namely phospholipid transfer protein (PLTP) and nicotinamide phosphoribosyltransferase (NAMPT) and elongation of long-chain fatty acids family member 5 (ELOVL5) through RNA sequencing and the unbiased systematic investigative approach. In addition, our experimental data indicated that LPC and PC metabolism were altered in ALD mice by using targeted metabolomics. PCR and WB showed that PLTP and NAMPT protein expression levels were ascended in the LKO_x005F_x0002_EtOH group than Flox-EtOH group in the ALD model group. At the same time, in ethanol-induced cell models, LPCAT3 overexpression upregulated ALT and TG levels, aggravated hepatocytes, damage and lipid production, and reduced the expression of PLTP and NAMPT. Conclusions: The results provide novel views on the significance of LPCAT3 in regulating liver phospholipid synthesis in the pathogenesis of ALD. Reduction of LPCAT3 in liver tissue is able to mitigate alcohol-induced hepatocyte damage and lipid production by regulating PLTP and NAMPT.
2025-01-10 | GSE273289 | GEO
Project description:Alcoholic liver disease, which varies in severity from mild steatosis to cirrhosis and hepatitis, is one of the most prevalent chronic liver diseases worldwide. Excessive alcohol consumption remains the leading cause of ALD and alcohol-related complications and deaths. However, no medications have been developed to treat this disease and its pathogenesis remains elusive. Here, to understand alcohol-induced AhR activation in more detail, transcriptomic data was conducted using livers from mice subjected to either control or Lieber-DeCarli alcohol diets.
2022-09-06 | GSE179398 | GEO
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
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