To investigate role of bile acids in modulating regulatory T cell phenotype under cholestatic conditions
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE237171 | GEO | 2025/10/30
REPOSITORIES: GEO
Similar Datasets
Project description:Regulatory T cells (Tregs) were shown to protect from cholestatic liver injury. Here we investigate whether amphiregulin (AREG), a ligand for epithelial growth factor receptor (EGFR) which promotes epithelial repair, mediates innate Treg functions in cholangiopathies. Mice were fed with diet containing 0.1 % of the xenobiotic 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) for 14 days to induce sclerosing cholangitis, followed by a 28-day recovery period (without DDC). Liver mononuclear and epithelial cells were enriched and subjected to single-cell sequencing at four time points: baseline, at day 14 of DDC treatment, and following a 14- or 28-day recovery period from 14 days of DDC treatment.
2025-12-31 | GSE230091 | GEO
Project description:Regulatory T cells (Tregs) were shown to protect from cholestatic liver injury. Here we investigate whether amphiregulin (AREG), a ligand for epithelial growth factor receptor (EGFR) which promotes epithelial repair, mediates innate Treg functions in cholangiopathies. Mice were fed with diet containing 0.1 % of the xenobiotic 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) for 14 days to induce sclerosing cholangitis, followed by a 28-day recovery period (without DDC). Liver mononuclear and epithelial cells were enriched and subjected to single-cell sequencing at six time points: baseline, at days 7 or 14 of DDC treatment, and following a 7-, 14- or 28-day recovery period from 14 days of DDC treatment.
2025-12-31 | GSE230085 | GEO
Project description:To investigate role of bile acids in modulating regulatory T cell phenotype under cholestatic conditions
| PRJNA994106 | ENA
Project description:Cholestatic injuries, featured with regional damage around the periportal, cause considerable mortality without curative therapies. It is technically challenging to dissect regional cell-cell interactions and molecular changes to fully understand cholangiopathies. Here, we generated a high-definition atlas of spatiotemporal transcriptome during cholestatic injury and repair. Remarkably, cholangiocytes functioned as a periportal hub by integrating signals from neighboring cells. We also dissected periportal damage, spatial heterogenous reprogramming and zonal regeneration, which appeared to be strongly associated with cholangiocyte. Moreover, spatiotemporal analyses revealed a key inhibitory rheostat for hepatocyte proliferation. Together, our study provides a comprehensive resource that is instrumental to demarcate regional cholestatic injury.
2022-12-02 | GSE219169 | GEO
Project description:Clinical disorders that impair bile flow result in retention of bile acids and cholestatic liver injury, characterized by parenchymal cell death, bile duct proliferation, liver inflammation and fibrosis. However, the pathogenic role of bile acids in the development of cholestatic liver injury remains incompletely understood. In this review, we summarize the current understanding of this process focusing on the experimental and clinical evidence for direct effects of bile acids on each major cellular component of the liver: hepatocytes, cholangiocytes, stellate cells and immune cells. During cholestasis bile acids accumulated in the liver, causing oxidative stress and mitochondrial injury in hepatocytes. The stressed hepatocytes respond by releasing inflammatory cytokines through activation of specific signaling pathways and transcription factors. The recruited neutrophils and other immune cells then cause parenchymal cell death. In addition, bile acids also stimulate the proliferation of cholangiocytes and stellate cells that are responsible for bile duct proliferation and liver fibrosis. This review explores the evidence for bile acid involvement in these phenomena. The role of bile acid receptors, TGR5, FXR and the sphingosine-1-phosphate receptor 2 and the inflammasome are also examined. We hope that better understanding of these pathologic effects will facilitate new strategies for treating cholestatic liver injury.
| S-EPMC8106037 | biostudies-literature
Project description:The goal of this study was to determine how thymic epithelial cells (TEC) differentiation and gene expression is affected by amphiregulin (AREG), which is produced by ILC2 upon thymic involution and the receptor for which is expressed by early TEC subsets. For this purpose we treated WT mice with recombinant AREG, sorted TEC from their thymi 10 days after treatment when the thymus is recovering and AREG has been released, and performed bulk RNA-Seq.
2024-01-11 | GSE244225 | GEO
Project description:Extrahepatic cholestasis leads to complex injury and repair processes that result in bile infarct formation, neutrophil infiltration, cholangiocyte and hepatocyte proliferation, extracellular matrix remodeling, and fibrosis. To identify early molecular mechanisms of injury and repair after bile duct obstruction, microarray analysis was performed on liver tissue 24 hours after bile duct ligation (BDL) or sham surgery. The most upregulated gene identified encodes plasminogen activator inhibitor 1 (PAI-1, Serpine 1), a protease inhibitor that blocks urokinase plasminogen activator (uPA) and tissue-type plasminogen activator (tPA) activity. Because PAI-1, uPA, and tPA influence growth factor and cytokine processing as well as extracellular matrix remodeling, we evaluated the role of PAI-1 in cholestatic liver injury by comparing the injury and repair processes in wild-type (WT) and PAI-1-deficient (PAI-1-/-) mice after BDL. PAI-1-/- mice had fewer and smaller bile infarcts, less neutrophil infiltration, and higher levels of cholangiocyte and hepatocyte proliferation than WT animals after BDL. Furthermore, PAI-1-/- mice had higher levels of tPA activation and mature hepatocyte growth factor (HGF) after BDL than WT mice, suggesting that PAI-1 effects on HGF activation critically influence cholestatic liver injury. This was further supported by elevated levels of c-Met and Akt phosphorylation in PAI-1-/- mice after BDL. In conclusion, PAI-1 deficiency reduces liver injury after BDL in mice. These data suggest that inhibiting PAI-1 might attenuate liver injury in cholestatic liver diseases. Total RNA isolated using TRI Reagent (Sigma, St. Louis, MO) was purified with an RNeasy mini kit (Qiagen, Valencia, CA). Twenty micrograms cRNA was hybridized to a mouse GeneChip (U74Av2, Affymetrix, Santa Clara, CA) at the Siteman Cancer Center GeneChip facility as described by the manufacturer. Analyses used one mouse per chip. Gene expression changes were analyzed using Affymetrix MicroArray Suite 4.0 and GeneChip 3.1 Expression Analysis and Statistical Algorithms (Affymetrix). The complete methodology and full data sets for all 6 analyzed chips are available at http://bioinformatics.wustl.edu.beckerproxy.wustl.edu This study compares the injury and repair processed in wild-type mice after BDL.
2011-06-09 | E-GEOD-29776 | biostudies-arrayexpress
Project description:Emerging evidence suggests the complex interactions between gut microbiota and bile acids, which are crucial end products of cholesterol metabolism. Cholestatic liver disease is characterized by dysfunction of bile production, secretion, and excretion, as well as excessive accumulation of potentially toxic bile acids. Given the importance of bile acid homeostasis, the complex mechanism of the bile acid-microbial network in cholestatic liver disease requires a thorough understanding. It is urgent to summarize the recent research progress in this field. In this review, we highlight how gut microbiota regulates bile acid metabolism, how bile acid pool shapes the bacterial community, and how their interactions contribute to the pathogenesis of cholestatic liver disease. These advances might provide a novel perspective for the development of potential therapeutic strategies that target the bile acid pathway.
| S-EPMC10222613 | biostudies-literature
Project description:Extrahepatic cholestasis leads to complex injury and repair processes that result in bile infarct formation, neutrophil infiltration, cholangiocyte and hepatocyte proliferation, extracellular matrix remodeling, and fibrosis. To identify early molecular mechanisms of injury and repair after bile duct obstruction, microarray analysis was performed on liver tissue 24 hours after bile duct ligation (BDL) or sham surgery. The most upregulated gene identified encodes plasminogen activator inhibitor 1 (PAI-1, Serpine 1), a protease inhibitor that blocks urokinase plasminogen activator (uPA) and tissue-type plasminogen activator (tPA) activity. Because PAI-1, uPA, and tPA influence growth factor and cytokine processing as well as extracellular matrix remodeling, we evaluated the role of PAI-1 in cholestatic liver injury by comparing the injury and repair processes in wild-type (WT) and PAI-1-deficient (PAI-1-/-) mice after BDL. PAI-1-/- mice had fewer and smaller bile infarcts, less neutrophil infiltration, and higher levels of cholangiocyte and hepatocyte proliferation than WT animals after BDL. Furthermore, PAI-1-/- mice had higher levels of tPA activation and mature hepatocyte growth factor (HGF) after BDL than WT mice, suggesting that PAI-1 effects on HGF activation critically influence cholestatic liver injury. This was further supported by elevated levels of c-Met and Akt phosphorylation in PAI-1-/- mice after BDL. In conclusion, PAI-1 deficiency reduces liver injury after BDL in mice. These data suggest that inhibiting PAI-1 might attenuate liver injury in cholestatic liver diseases.
2011-06-09 | GSE29776 | GEO
Project description:Bile acids are potent antibacterial compounds and play an important role in shaping the microbial ecology of the gut. Here, we combined flow cytometry, growth rate measurements (OD600), and NMR- and mass spectrometry-based metabolomics to systematically profile the impact of bile acids on the microbiome using in vitro and in vivo models. This study confirmed that (1) unconjugated bile acids possess more potent antibacterial activity than conjugated bile acids; (2) Gram-positive bacteria are more sensitive to bile acids than Gram-negative bacteria; (3) some probiotic bacteria such as Lactobacillus and Bifidobacterium and 7α-dehydroxylating bacteria such as Clostridium scindens show bile acid resistance that is associated with activation of glycolysis. Moreover, we demonstrated that (4) as one of most hydrophobic bile acids, lithocholic acid (LCA) shows reduced toxicity to bacteria in the cecal microbiome in both in vivo and in vitro models; (5) bile acids directly and rapidly affect bacterial global metabolism including membrane damage, disrupted amino acid, nucleotide, and carbohydrate metabolism; and (6) in vivo, short-term exposure to bile acids significantly affected host metabolism via alterations of the bacterial community structure. This study systematically profiled interactions between bile acids and gut bacteria providing validation of previous observation and new insights into the interaction of bile acids with the microbiome and mechanisms related to bile acid tolerance.
| S-EPMC7524280 | biostudies-literature