Mouse gut metagenome
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA794745 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:SNP array of 7 HCCs and matched background liver in children with bile salt export pump deficiency
| EGAD00010000560 | EGA
Project description:Whole exome sequencing of 6 HCCs and matched background liver in children with bile salt export pump deficiency.
| EGAD00001000811 | EGA
Project description:Hepatic fibrosis, the wound-healing response to repeated liver injury, ultimately leads to cirrhosis. There is an urgent need to develop effective antifibrotic therapies. Ghrelin (encoded by Ghrl) is an orexigenic hormone that has pleiotrophic functions including protection against cell death1. Here we investigate whether ghrelin modulates liver fibrosis and protects from acute liver injury. Recombinant ghrelin reduced the fibrogenic response to prolonged bile duct ligation in rats. This effect was associated with decreased liver injury and myofibroblast accumulation as well as attenuation of the altered gene expression profile. Ghrelin also reduced fibrogenic properties in cultured hepatic stellate cells. Moreover, Ghrl-/- mice developed exacerbated hepatic fibrosis and liver damage after chronic injury. Ghrelin also protected rat livers from acute liver injury and reduced the extent of oxidative stress and the inflammatory response. In patients with chronic liver diseases, ghrelin serum levels decreased in those with advanced fibrosis and hepatic expression of the ghrelin gene correlated with expression of fibrogenic genes. Finally, in patients with chronic hepatitis C, single nucleotide polymorphisms of the ghrelin gene (-994CT and â604GA) influenced the progression of liver fibrosis. We conclude that ghrelin exerts antifibrotic effects on the liver and may represent a novel antifibrotic therapy. Experiment Overall Design: Rats were divided into three groups: control rats receiving saline (sham operation), rats with bile duct ligation receiving saline and rats with bile duct ligation receiving recombinant ghrelin (10 micrograms/Kg/day by a subcutaneous osmotic mimi-pump). For the microarray analysis samples from 6 rats were analyzed except for the ghrelin-treated group (5 rats).
2009-01-13 | E-GEOD-13747 | biostudies-arrayexpress
Project description:Massive gene amplification drives pediatric hepatocellular carcinoma caused by bile salt export pump deficiency
| PRJNA243011 | ENA
Project description:Hepatic cell lines serve as economical and reproducible alternatives for primary human hepatocytes. However, the utility of hepatic cell lines to examine bile acid homeostasis and cholestatic toxicity is limited due to abnormal expression and function of bile acid-metabolizing enzymes, transporters, and the absence of canalicular formation. Previously, addition of dexamethasone (DEX) and Matrigel™ overlay restored expression, localization, and function of the bile salt export pump (BSEP), and formation of bile canalicular-like structures in four-week cultures of HuH-7 human hepatoma cells. We present here an improved differentiation process with the addition of 0.5% dimethyl sulfoxide (DMSO), which increased the expression and function of the major bile acid uptake and efflux transporters, sodium taurocholate co-transporting polypeptide (NTCP) and BSEP, respectively, in two-week HuH-7 cell cultures. This in vitro model was further characterized for expression of cytochrome P450 enzymes (CYP450s), uridine 5'-diphospho-glucuronosyltransferase (UGTs) and transporters using quantitative targeted proteomics.
2022-10-14 | PXD031731 | Pride
Project description:Background and aims: Signal transducer and activator of transcription 3 (Stat3) is the main mediator of interleukin-6 type cytokine signaling required for hepatocyte proliferation and hepatoprotection but its role in sclerosing cholangitis and other cholestatic liver diseases remains unresolved. Methods: We investigated the role of Stat3 in inflammation-induced cholestatic liver injury and used mice lacking the multidrug resistance gene 2 (mdr2-/-) as a model for SC. Results: We demonstrate that conditional inactivation of stat3 in hepatocytes and cholangiocytes (stat3 delta hc) of mdr2-/- mice strongly aggravated bile acid-induced liver injury and fibrosis. A similar phenotype was observed in mdr2-/- mice lacking IL-6 production. Biochemical and molecular characterization suggested that Stat3 exerts hepatoprotective functions in both, hepatocytes and cholangiocytes. Loss of Stat3 in cholangiocytes led to increased expression of TNFα which might reduce the barrier function of bile ducts. Loss of Stat3 in hepatocytes led to upregulation of bile acid biosynthesis genes and downregulation of hepatoprotective epidermal growth factor receptor and insulin-like growth factor 1 signaling pathways. Consistently, stat3deltahc mice were more sensitive to cholic acid-induced liver damage than control mice. Conclusions: Our data suggest that Stat3 prevents cholestasis and liver damage in sclerosing cholangitis via regulation of pivotal functions in hepatocytes and cholangiocytes. Affymetrix microarray analyses was performed to identify metabolic and molecular pathways in stat3Dhc mdr2-/- mice that lead to cholestasis and bile acid-induced liver injury. To avoid false positive results that are due to differential cellular composition, we defined the onset of fibrosis and expression of fibrogenic factors in stat3Dhc mdr2-/- mice.
2010-10-20 | E-GEOD-18759 | biostudies-arrayexpress
Project description:DY131 is a pharmacological agonist of the orphan receptor estrogen-related receptor (ERR) γ which plays a crucial role in regulating energy generation, oxidative metabolism, cell apoptosis, inflammatory responses, etc. However, its role in acute liver injury is unknown. In the study, we evaluated the effect of DY131 on lipopolysaccharide (LPS)-induced liver injury. Transcriptomics analysis revealed that the dysregulated pathways associated with inflammation and metabolism were significantly reversed by DY131 in LPS-treated mice, providing more evidence in favor of the protective effect of DY131 against LPS-induced liver injury.
2020-11-06 | GSE160880 | GEO
Project description:The Th2 cytokine IL-13 has been described to be involved in biliary epithelial injury and liver fibrosis in patients as well as in animal models. IL-13 was found to reduce tight junction-associated barrier function of bile ducts, to promote cholangiocyte hyperplasia, and thus causing biliary epithelial injury. We generated Abcb4-/-- and IL-13-/- double-knockout mice on fibrosis susceptible genetic background BALB/c. Molecular and cellular mechanisms of hepatic and ileal pathology were investigated by mRNA microarray. Depletion of IL-13 in Abcb4-/--mice resulted in a tenfold decrease of total serum bile acid concentrations at the age of 8 weeks and lead to a recovery of intrahepatic bile duct integrity. The decrease of serum bile acid in 8 week old mice went along with relative enhancement of bile acid excretion and normalization of the composition of fecal bile excretion, correction of fecal microbiome, and improved ileal integrity. Liver integrity, measured by serum ALT, was ameliorated in younger mice and strongly correlated with the concentration of serum bile acids. 52 weeks old Abcb4-/-IL-13-/--mice exhibited significantly reduced hepatic fibrosis.
2020-11-02 | GSE90995 | GEO
Project description:Alterations in the gastrointestinal microbiota have been implicated in obesity in mice and humans, but the conserved microbial functions that influence host energy metabolism and adiposity have not been determined. Here we show that bacterial bile salt hydrolase (BSH) controls a microbe-host dialogue which functionally regulates host lipid metabolism and weight gain. Expression of cloned BSH enzymes in the GI tract of gnotobiotic or conventional mice significantly altered plasma bile acid signatures and regulated transcription of key genes involved in lipid metabolism (PPARgamma angptl4), cholesterol metabolism (abcg5/8), gastrointestinal homeostasis (regIIIgamma) and circadian rhythm (dbp, per1/2) in the liver or small intestine. High-level expression of BSH in conventionally raised mice resulted in significant reduction of host weight-gain, plasma cholesterol and liver triglycerides. We demonstrate that bacterial BSH activity significantly impacts systemic metabolic processes and adiposity in the host, and represents a key mechanistic target for the control of obesity and hypercholesterolaemia. Germ free Swiss Webster mice were monocolonised with EC containing the bacterial gene, Bile salt hydroalse. The treatment groups and relevant controls were; 1. Germ Free(GF) n=4 , 2. GF and EC n=4, 3. GF and EC +BSH1 n=4, 4. GF and EC+ BSH2 n=4, 5. GF re-conventionalised (CONV-D) n= 5. The Ileum and Liver were removed and the RNA extracted (RNAeasy plus universal kit (Qiagen), quantified and Microarrays were carried out using mouse Exon ST1.0 arrays (Affymetrix) by Almac Group, Craigavon, Northern Ireland. Analysis and pathway mapping was carried out by ALMAC and using Subio Platform software (Subio Inc) and Genesis Software.
2014-05-09 | E-GEOD-46952 | biostudies-arrayexpress
Project description:Chimeric mice with humanized livers are considered a useful animal model for predicting human drug metabolism and toxicity. In this study, the characteristics of fresh h-hepatocytes (cFHHs, PXB-cells®) isolated from chimeric mice (PXB-mice®) were evaluated in vitro to confirm their utility for drug development. The cFHHs cultured at high density (2.13 × 10^5 cells/cm2) displayed stable production of human albumin and cytochrome P450 (CYP) 3A activities for at least 21 days. The mRNA expression levels of 10 of 13 CYPs, UDP-glucuronosyltransferase (UGP), and transporters were maintained at >10% of the levels of freshly isolated cFHHs after 21 days. From 7-days cultured cFHHs at high density, many bile canaliculi were observed between cFHHs, and the accumulation of multidrug resistance-associated protein (MRP2) and bile salt export pump (BSEP) substrates in these bile canaliculi was clearly inhibited by cyclosporin A. We used microarrays to elucidate global gene expressions underlying this higher hepatic functions of high density cultured cFHHs (PXB-cells). Microarray analysis revealed that high density cultured cFHHs maintained high expressions of some transcription factors (HNF4α, PXR, and FXR) perhaps involved in the high CYP, UGT and transporter gene expressions of cFHHs.
2020-08-07 | GSE153298 | GEO