NLRP6 in ALD mouse model (A08)
Ontology highlight
ABSTRACT:
PROVIDER: PRJEB48802 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| ERR7416750_1.fastq.gz | Fastqsanger.gz | |||
| ERR7416750_2.fastq.gz | Fastqsanger.gz | |||
| ERR7416760_1.fastq.gz | Fastqsanger.gz | |||
| ERR7416760_2.fastq.gz | Fastqsanger.gz | |||
| ERR7416770_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 44 |
Similar Datasets
Project description:Alcoholic liver disease is a pathological condition caused by over-consumption of alcohol. Due to the high prevalence of morbidity and mortality associated with this disease, there remains a need to elucidate the molecular mechanisms underlying the etiology to develop new treatments. Since peroxisome proliferator-activated receptor-β/δ (PPARβ/δ) modulates ethanol-induced hepatic effects, the present study examined alterations in gene expression that may contribute to this disease.
2017-01-04 | GSE86002 | GEO
Project description:Estrogen receptor β (ERβ) and NOD-, LRR- and pyrin domain-containing 6 (NLRP6) are highly expressed in intestinal tissues and reduce intestinal inflammation, but their underlying mechanisms are unclear. We found that ERβ and NLRP6 levels were reduced in patients with inflammatory bowel disease (IBD), and that deletion of ERβ or NLRP6 was exacerbated colitis in mouse models. We discovered that ERβ exerted its anti-inflammatory activity by inducing NLRP6-mediated autophagy. Specifically, ERβ directly regulated NLRP6 gene expression and NLRP6 inflammasome activation through genomic and non-genomic effects. NLRP6 directly interacted with multiple autophagy-related proteins (including ULK1, BECN1, ATG5-ATG12-ATG16L1 complex, p62, and PHB2). Autophagy stimulation suppresses the inflammatory response by eliminating excess ERβ, NLRP6, ASC, Casp-1, IL-1β, TNF-α and damaged mitochondria. These findings indicate that ERβ-NLRP6-autophagy forms a negative feedback loop to maintain intestinal epithelial cell homeostasis and facilitate tissue repair.
2023-06-05 | GSE151864 | GEO
Project description:Alcoholic liver diseases (ALDs) encompass a broad spectrum of clinical features of alcoholic fatty liver, alcoholic steatohepatitis and cirrhosis, and increased risk of hepatocellular carcinoma. While the toxic effects of alcohol likely result from complex interactions between genes and the environment, the molecular mechanisms of alcohol-induced liver damage remains undefined. Thus, a better understanding of the mechanisms regulating hepatic cell injury may lead to more effective therapeutic approaches for ALD. Here we compared the miRNA expression profile from tissues from control mice and mice receiving intragastric ethanol feeding. Four microarray hybridization studies were performed on three different pairs of liver-derived RNA from intragastric ethanol feeding and normal mice. The miRNAs differentially overexpressed in livers from ethanol fed mice.
2014-10-07 | E-MTAB-2311 | biostudies-arrayexpress
Project description:Purpose: The goals of this study are to use NGS-derived liver transcriptome profiling (RNA-seq) and identify differentially expressed genes in damaged livers that were exposed to 5% ethanol-containing liquid diet and ethanol binge. Methods: Liver mRNA profiles were generated from chronic ethanol feeding plus a single binge by deep sequencing, in duplicate, using Illumina Hiseq2500. qRT–PCR validation was performed using SYBR Green assay. Results: Chronic ethanol feeding plus a single binge treatment was associated with 422 downregulated genes and 384 upregulated genes, whereas Yap1 null livers had 351 downregulated genes and 287 upregulated genes after ethanol/CCl4 induced liver damage. Conclusions: This study provides detailed analysis of liver transcriptomes during hepatocyte damage caused by chronic ethanol feeding plus a single binge treatment, with biologic replicates, generated by RNA-seq technology.
2022-02-10 | GSE196314 | GEO
Project description:Nlrp6 inflammasome and colonic inner mucus layer function
| PRJEB30844 | ENA
Project description:To investigate the function of mitochondrial fission protein DRP1 in the development of alcoholic liver disease, we generated liver-specific Dnm1l KO mice using Alb-Cre/loxP system. These mice were subjected to Gao-Binge alcohol model. We then performed RNA sequensing analysis using the liver tissue. Gene expression profiling analysis was conducted using data obtained from RNA-seq of 4 different groups.
2022-07-01 | GSE207074 | GEO
Project description:Intrahepatic neutrophil infiltration has been implicated in the pathogenesis of severe alcoholic hepatitis (SAH), a disease with high short-term morality; however, how neutrophils contribute to SAH progression remain obscure. This study aimed to characterize intrahepatic neutrophil infiltration and its involvement in AH pathogenesis. We found that hepatic expression of neutrophil cytosolic factor 1 (NCF1), a key factor in controlling neutrophilic ROS production, was upregulated and correlated with neutrophil number, inflammation and ROS-associated genes in SAH patients. Ncf1 floxed mice were generated using CRISPR/Cas9 technology by inserting two LoxP sequences into intron 1 and intron 8 of the mouse Ncf1 gene, then crossed with Lyz Cre mice to generated myeloid cell-specific Ncf1 knockout (Ncf1Lyz-/-) mice. The LyzCre negative Ncf1 floxed mice were used as corresponding WT littermate control. The chronic-plus-binge ethanol feeding model was used in this study. The total RNAs were extracted from ETOH-fed 5 WT and 4 Ncf1Lyz-/- mouse livers and submitted for a Poly(A) RNA sequencing. Genetic deletion of the Ncf1 gene in neutrophils abolished hepatic ROS, inflammation, and fibrosis induced by ethanol feeding. RNA-sequencing analysis and the data from experimental models revealed that neutrophilic NCF1-dependent ROS promoted alcoholic liver injury by inhibiting AMP-activated protein kinase (a key regulator of lipid metabolism) and microRNA-223 (a key anti-inflammatory and anti-fibrotic microRNA). Our data suggest that divergent pathogeneses exist in SAH and neutrophilic NCF1-dependent ROS promotes alcoholic liver injury by inhibiting AMPK and microRNA-223.
2022-07-16 | GSE192720 | GEO
Project description:Alcoholic hepatitis (AH) continues to be a disease with high mortality and no efficacious medical treatment. Although severe AH is presented as acute on chronic liver failure, what underlies this transition from chronic alcoholic steatohepatitis (ASH) to AH, is largely unknown. To address this question, unbiased RNA-seq and proteomic analyses were performed on livers of the recently developed AH mouse model which exhibits the shift to AH from chronic ASH upon weekly alcohol binge, and these results are compared with gene expression profiling data from AH patients. This cross-analysis has identified Casp11 (CASP4 in man) as a commonly upregulated gene known to be involved in non-canonical inflammasome pathway. Immunoblotting confirms CASP11/4 activation in AH mice but not in chronic ASH. Gasdermin-D (GSDMD) which induces pyroptosis (lytic cell death caused by bacterial infection) downstream of CASP11/4 activation, is also activated in AH livers. CASP11 deficiency reduces GSDMD activation, bacterial load in the liver, and the severity of AH. Conversely, the deficiency of IL-18, the key anti-microbial cytokine, aggravates hepatic bacterial load, GSDMD activation, and AH. Further, hepatocyte-specific expression of constitutively active GSDMD worsens hepatocellular lytic death and PMN inflammation. These results implicate pyroptosis induced by CASP11/4-GSDMD pathway in the pathogenesis of AH.
2017-03-31 | GSE97234 | GEO
Project description:Nlrp6-/- lamina propria Ly6C-hi monocytes in response to AOM/DSS have deficient TNFα production, but increased production of other pro-inflammatory cytokines as compared to WT NLRP6 is a member of the Nod-like receptor family, whose members are involved in the recognition of microbes and/or tissue injury. NLRP6 was previously demonstrated to regulate the production of IL-18 and is important for protecting mice against chemically-induced intestinal injury and colitis-associated colon cancer. However, the cellular mechanisms by which NLRP6 reduces susceptibility to colonic inflammation remain unclear. Here, we determined that NLRP6 expression is specifically upregulated in Ly6Chi inflammatory monocytes that infiltrate into the colon during dextran sulfate sodium (DSS)-induced inflammation. Adoptive transfer of WT Ly6Chi inflammatory monocytes into Nlrp6-/- mice was sufficient to protect them from mortality, significantly reducing intestinal permeability and damage. NLRP6-deficient inflammatory monocytes were specifically defective in TNFα production, which was important for reducing DSS-induced mortality and dependent on autocrine IL-18 signaling by inflammatory monocytes. Our data reveal a previously unappreciated role for NLRP6 in inflammatory monocytes, which are recruited during intestinal injury to promote barrier function and limit bacteria-driven inflammation. This study also highlights the importance of early cytokine responses, particularly NLRP6-dependent and IL-18-dependent TNFα production in preventing chronic dysregulated inflammation. Ly6Chi monocytes were sorted from lamina propria of WT or Nlrp6-/- mice at day 10 of AOM/2%DSS. RNA was extracted and hybridized to the mouse 2.1 ST array.
2016-03-27 | E-GEOD-79631 | biostudies-arrayexpress
Project description:Global gene expression patterns of 2 human steatosis and 9 human non-alcoholic steatohepatitis (NASH) together with their respective control patterns were analyzed to define the non-alcoholic fatty liver disease (NAFLD) progression molecular characteristics and to define NASH early markers from steatosis. Human liver samples of steatosis and non-alcoholic steatohepatitis were selected for RNA extraction and hybridization on Affymetrix microarrays. This dataset is part of the TransQST collection.
2014-11-07 | E-GEOD-63067 | biostudies-arrayexpress