Protection by Jia-Ga-Song-Tang from Alcohol-induced Liver and Intestines damage
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus Musculus
SUBMITTER: 
Tianqin Xiong
PROVIDER: PXD034952 | iProX | Tue Jun 28 00:00:00 BST 2022
REPOSITORIES: iProX
Publications
Jia-ga-song-tang protection against alcoholic liver and intestinal damage.
Fang Jiamin J Wu Yuhuan Y Gan Changlian C Ruan Shufang S He Xiaoliang X Wang Bixia B Wang Ying Y Yu Jingtao J Sang Chuanlan C Zeren Dawa D Xiong Tianqin T
Frontiers in pharmacology 20220926
Gut-liver axis and cellular homeostasis play key roles in alcohol liver disease (ALD). Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is a stress-sensitive guarantor of cellular homeostasis. We investigated whether the beneficial effects and underlying mechanisms of Jia-ga-song Tang (JGST) against ALD were associated with gut-liver axis and cellular homeostasis. A predictive network depicting the relationship between Jia-Ga-Song-Tang (JGST) and alcoholic liver disease (ALD) was designed by N ...[more]
Similar Datasets
Project description:Nicotinamide mononucleotide adenylyltransferase 1 (NMNAT1), an NAD+ synthetase in Preiss-Handler and salvage pathways, governs nuclear NAD+ homeostasis. This study investigated the role of NMNAT1 on alcohol-associated liver disease (ALD). Decreased NMNAT1 expression and activity were observed in the liver of alcohol-associated hepatitis patients and either liver or primary hepatocytes from ALD mice. F-box and WD repeat domain containing 7 (FBXW7)-regulated interferon regulatory factor 1 (IRF1) ubiquitination degradation contributed to alcohol-inhibited NMNAT1 transcriptional level. Hepatic NMNAT1 knockout aggravated alcohol-induced hepatic NAD+ decline and further hepatic steatosis and liver injury. Metabolomics and transcriptomics interaction revealed that cysteine sulfinic acid decarboxylase (CSAD)-regulated taurine pathway was involved in NMNAT1-disrupted hepatic lipid metabolism in ALD. Hepatic CSAD overexpression or taurine supply attenuated hepatic NMNAT1 knockout-aggravated ALD, respectively. Hepatic NMNAT1 loss inhibited NMN-protected ALD. Replenishing hepatic NMNAT1 reversed liver lipid accumulation in ALD mice. These findings identified NMNAT1 as a promising therapeutic target for ALD.
2025-05-25 | GSE297696 | GEO
Project description:Alcohol is metabolized in the liver, and chronic consumption can lead to inflammation, scarring, and damage to liver cells. The pathogenesis of alcoholic liver disease (ALD), a complicated condition, is characterized by a succession of histopathological alterations that occur through a multistep and multifactorial process. FAF2/UBXD8/ETEA is a ubiquitin ligase adaptor protein and plays a crucial role in the ubiquitin-mediated degradation of misfolded proteins in the endoplasmic reticulum. Recent GWAS study indicated that FAF2 was associated with ALD, but the exact function of FAF2 in ALD has not been identified yet. The objective of this study was to investigate the role of FAF2 in ALD.Our study revealed a noteworthy rise in hepatic FAF2 protein expression among individuals with ALD and mice subjected to chronic-plus-single binge ethanol feeding. The suppression of FAF2 in mice liver provided protection against alcohol-induced hepatic steatosis.
2025-02-26 | GSE270659 | GEO
Project description:Alcohol-related liver disease (ALD) involves inflammation, hepatocellular damage, and fibrosis. Apolipoprotein E (Apoe) plays a role in immune regulation and tissue repair, but its function in ALD remains unclear. To explore this, we performed RNA sequencing on liver tissues from wild-type (WT) and Apoe knockout (Apoe KO) mice subjected to a chronic-plus-binge ethanol model. Gene expression analysis revealed distinct clustering between groups and significant alterations in pathways related to neutrophil degranulation, extracellular matrix organization, and collagen formation, indicating heightened inflammation and fibrosis in Apoe KO mice. These findings offer insights into Apoe’s role in ALD and liver repair.
2025-03-17 | GSE292193 | GEO
Project description:Alcohol-related liver disease (ALD) is a leading cause of liver-related mortality worldwide, with limited treatment options beyond abstinence and liver transplantation. Chronic alcohol consumption has been linked to magnesium (Mg2+) deficiency, which can influence the liver disease progression. The mechanisms underlying Mg2+ homeostasis dysregulation in ALD remain elusive. This study aimed to investigate the role of the Mg2+ transporter Cyclin M4 (CNNM4) in ALD by analyzing its expression patterns in ALD patients and preclinical animal models. In this study, CNNM4 is upregulated in the liver of both ALD patients and animal models. CNNM4 overexpression triggers Mg²⁺ homeostasis dysregulation, linked to ALD progression. We propose a novel therapeutic approach for ALD treatment using N-acetylgalactosamine (GalNAc) silencing RNA (siRNA) technology to specifically modulate Cnnm4 expression in the liver, improving mitochondrial function and alleviating ER stress. Notably, silencing Cnnm4 restores protein isoaspartyl methyltransferase (PCMT1) activity, essential for repairing ethanol-induced protein damage. Enhancing mitochondrial activity through Cnnm4-dependent mechanisms increases SAMe levels, crucial for PCMT1 function, highlighting the interconnected roles of mitochondrial health and protein homeostasis in ALD treatment. These findings shed light on the dysregulation of Mg2+ homeostasis in ALD, providing a promising therapeutic approach targeting CNNM4. GalNAc siCnnm4 therapy boost the repair processes of ethanol damaged proteins through the upregulation of PCMT1 activity.
2025-07-21 | PXD058781 | Pride
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: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 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:Chronic alcohol abuse has a detrimental effect on the brain and liver. There is no effective treatment for these patients and the mechanism underlying alcohol addiction and consequent alcohol-induced damage of the liver/brain axis remains unresolved. We compared experimental models of alcoholic liver disease (ALD) and alcohol dependence in mice and demonstrated that genetic ablation of IL17 Receptor A (IL17ra-/-), or pharmacological blockade of IL17 signaling effectively suppressed the increased voluntary alcohol drinking in alcohol-dependent mice, and blocked alcohol-induced hepatocellular and neurological damage. The level of circulating IL17A positively correlated with the alcohol use in excessive drinkers, and was further increased in patients with ALD as compared to healthy individuals. Our data suggest that IL17A is a common mediator of excessive alcohol consumption and alcohol-induced liver/brain injury, and targeting IL17A may provide a novel strategy for treatment of alcohol-induced pathology.
2020-04-07 | GSE137228 | 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:Background & Aims: Liver macrophages are heterogeneous and play an important role in alcohol_x0002_associated liver disease (ALD) but there is limited understanding of the functions of specific macrophage subsets in the disease. We used a Western Diet Alcohol (WDA) mouse model of ALD to examine the hepatic myeloid cell compartment by scRNA seq and targeted Kupffer cell (KC) ablation to understand the diversity and function of liver macrophages in ALD. Approach and Results: In the WDA liver, KCs and infiltrating monocytes/macrophages (IMs) each represented about 50% of the myeloid pool. Five major KC clusters all expressed genes associated with receptor mediated endocytosis and lipid metabolism, but most were predicted to be non_x0002_inflammatory and antifibrotic with one minor KC cluster having a pro-inflammatory and extracellular matrix degradation gene signature. IM clusters, in contrast, were predicted to be pro_x0002_inflammatory and pro-fibrotic. In vivo diphtheria toxin based selective KC ablation during alcohol exposure resulted in a liver failure phenotype with increases in PT/INR and bilirubin, loss of differentiated hepatocyte gene expression, and an increase in expression of hepatocyte progenitor markers such as EpCAM, CK-7 and Igf2bp3. Gene set enrichment analysis of whole liver RNAseq from the KC ablated WDA mice showed a similar pattern as seen in human alcoholic hepatitis. Conclusions: In this ALD model, KCs are anti-inflammatory and are critical for maintenance of hepatocyte differentiation. IMs are largely pro-inflammatory and contribute more to liver fibrosis. Future targeting of specific macrophage subsets may provide new approaches to treatment of liver failure and fibrosis in ALD.
2024-10-25 | GSE269059 | GEO