Comprehensive gene expression profile of extrahepatic bile ducts in mice with experimental biliary atresia
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE46967 | GEO | 2013/06/01
SECONDARY ACCESSION(S): PRJNA203252
REPOSITORIES: GEO
Similar Datasets
Project description:Newborn Balb/c mice were injected intraperitoneally with 1.5x10^6 fluorescent-forming units (ffu) of type- A Rhesus Rotavirus (RRV) or 0.9% normal saline (NS; control) within 24 hours of birth to induce experimental model of biliary atresia. Extrahepatic bile ducts including gallbladder were microdissected en bloc at 3, 7 and 14 days after RRV or saline injections. GeneChipM-BM-. Mouse Gene 1.0 ST Array (Affymetrix, CA) were used to screen mRNAs whose expression was differently regulated after RRV challenge compared to normal saline controls. Gene expression profiling: Each experimental conditon contains 3 sets of samples. Each sample consists of two to six extrahepatic bile ducts pooled prior to isolation of total RNA to ensure generation of adequate mRNA to perform quantitative experiments.
2013-06-01 | E-GEOD-46967 | biostudies-arrayexpress
Project description:Newborn Balb/c mice were injected with 1.5x10^6 fluorescent-forming units (ffu) of Rhesus rotavirus type-A or 0.9% NaCl (normal saline) intraperitoneally within 24 hours of birth to induce experimental model of biliary atresia. The extrahepatic bile ducts including gallbladder were microdissected en bloc at 3, 7 and 14 days after rhesus rotavirus or saline injection. GeneChip® Mouse Gene 1.0 ST Array (Affymetrix, CA) were used to screen mRNAs whose expression was differently regulated after rhusus rotavirus injection compare to the normal saline controls.
2013-10-15 | GSE41594 | GEO
Project description:Newborn Balb/c mice were injected with 1.5x10^6 fluorescent-forming units (ffu) of Rhesus rotavirus type-A or 0.9% NaCl (normal saline) intraperitoneally within 24 hours of birth to induce experimental model of biliary atresia. The extrahepatic bile ducts including gallbladder were microdissected en bloc at 3, 7 and 14 days after rhesus rotavirus or saline injection. TaqMan® Array Rodent MicroRNA Card v2.0 (A and B) were used to screen microRNAs whose expression was differently regulated after rhusus rotavirus injection compare to the normal saline controls.
2013-10-15 | GSE41593 | GEO
Project description:Newborn Balb/c mice were injected with 1.5x10^6 fluorescent-forming units (ffu) of Rhesus rotavirus type-A or 0.9% NaCl (normal saline) intraperitoneally within 24 hours of birth to induce experimental model of biliary atresia. The extrahepatic bile ducts including gallbladder were microdissected en bloc at 3, 7 and 14 days after rhesus rotavirus or saline injection. GeneChipM-BM-. Mouse Gene 1.0 ST Array (Affymetrix, CA) were used to screen mRNAs whose expression was differently regulated after rhusus rotavirus injection compare to the normal saline controls. Gene expression profiling. Each experimental conditon has 3 sets of samples . Two to six extrahepatic bileducts were pooled prior to isolating total RNA depending on the size to ensure adequate RNA quantities to perform experiments quantifying mRNA expression.
2013-10-15 | E-GEOD-41594 | biostudies-arrayexpress
Project description:Newborn Balb/c mice were injected with 1.5x10^6 fluorescent-forming units (ffu) of Rhesus rotavirus type-A or 0.9% NaCl (normal saline) intraperitoneally within 24 hours of birth to induce experimental model of biliary atresia. The extrahepatic bile ducts including gallbladder were microdissected en bloc at 3, 7 and 14 days after rhesus rotavirus or saline injection. TaqManM-BM-. Array Rodent MicroRNA Card v2.0 (A and B) were used to screen microRNAs whose expression was differently regulated after rhusus rotavirus injection compare to the normal saline controls. microRNA expression profiling. Each experimental conditon has 3 sets samples . Two to six extrahepatic bileducts were pooled prior to total RNA isolation depending on the size to ensure adequate RNA quantities to perform experiments quantifying microRNA expression.
2013-10-15 | E-GEOD-41593 | biostudies-arrayexpress
Project description:Biliary atresia (BA) is a rare cholestatic disease of unknown etiology that affects infants and shows an incidence of 1 out of 18,000 live births in Europe (1). The first therapeutic option is a timely performed portoenterostomy. However, the majority of patients suffer from a progressive inflammatory process, which leads to complete destruction of the extra- and intrahepatic biliary system followed by end-stage liver cirrhosis. Hence, BA is the leading indication for pediatric liver transplantation worldwide (2, 3). To understand the pathogenesis of the disease and improve theoutcome of BA patients, research has focused on the inflammatory process in liver and bile ducts, in which several factors are remarkably elevated, such as activated CD4 and CD8 T-cells, TNF alpha,IFN alpha and other proinflammatory TH1 cytokines (3-8). By the time of diagnosis, however, the disease has already reached an advanced state, characterized by the complete obstruction of the extrahepatic bile ducts with impaired bile flow and fibrosis or cirrhosis of the liver. Therefore, studies in humans focusing on the trigger mechanism of BA are limited due to the paucity of liver and availability of bile duct tissue for research. One infectious animal model has been developed, in which newborn Balb/c mice exclusively show the experimental BA phenotype after infection with rhesus rotavirus (RRV) (9, 10). This model allows the analysis of the inflammatory reactions in liver and bile ducts at early steps in the development of bile duct atresia (11-20). Furthermore, inbred mouse strains have been shown to have a different susceptibility for the development of experimental BA, suggesting that Balb/c mice have an immunological gap responsible for disease progression (10, 12). The aim of this study was to identify key genes responsible for the BA phenotype by comparing the transcriptomes at an early time point after virus infection, i.e. before bile duct atresia, between two mouse strains with different susceptibilities to BA. Differences in the virus titration and the clinical course of infected mice were analyzed, and variations in the hepatic gene response assessed by comparative microarray assays were correlated to variances in the hepatic inflammatory reaction. Balb/c mice and C57Black/6 (Black/6) mice were infected with RRV postpartum and signs of BA and survival were noted. Liver sections of diseased, healthy and control animals were assessed for T-cell expression, and the virus loads were determined. Second, mice were sacrificed after three days, and isolated hepatic RNA was subjected to gene expression analysis using Affymetrix Gene Chip MOE 430 2.0.We compared three individual expression profiles from RRV-infected Balb/c mice against 2 individual expression profiles from RRV-infected C57/BL6 control mice using the Affymetrix GeneChip MOE 430 2.0.
2009-08-30 | E-GEOD-13245 | biostudies-arrayexpress
Project description:Hepatic microRNA was measured by Exiqon array in the mouse RRV model of biliary atresia miRNA expression profiling. For the miRNA microarray experiment, RRV and saline injected animals were euthanized at 3, 8, and 14 days post infection (n=5 per treatment, per time point), and total RNA was purified from liver using the mirVana miRNA Isolation Kit (Ambion) according to the manufacturer's instructions. A pooled common control was assembled from an equal RNA mass from each of the samples, and samples and control were separately dye-labeled, and hybridized to a miRcury v11.0 miRNA microarray (Exiqon) at the University of Pennsylvania School of Medicine Microarray core facility. Sample hybridization intensities were scored relative to the common control, and raw intensity data were normalized and analyzed using the SAM add-in for Microsoft Excel. MiRNAs exhibiting a fold-change of greater than 10% up or down, at a false discovery rate of 5% were chosen for further study.
2011-11-04 | GSE33418 | GEO
Project description:Hepatic microRNA was measured by Exiqon array in the mouse RRV model of biliary atresia miRNA expression profiling. For the miRNA microarray experiment, RRV and saline injected animals were euthanized at 3, 8, and 14 days post infection (n=5 per treatment, per time point), and total RNA was purified from liver using the mirVana miRNA Isolation Kit (Ambion) according to the manufacturer's instructions. A pooled common control was assembled from an equal RNA mass from each of the samples, and samples and control were separately dye-labeled, and hybridized to a miRcury v11.0 miRNA microarray (Exiqon) at the University of Pennsylvania School of Medicine Microarray core facility. Sample hybridization intensities were scored relative to the common control, and raw intensity data were normalized and analyzed using the SAM add-in for Microsoft Excel. MiRNAs exhibiting a fold-change of greater than 10% up or down, at a false discovery rate of 5% were chosen for further study. Three time points (3, 8, 14 days) x 2 conditions x 6 replicates - 1 failed sample = 35 samples
2011-11-04 | E-GEOD-33418 | biostudies-arrayexpress
Project description:The etiology and pathogenesis of bile duct obstruction in children with biliary atresia are largely unknown. We have previously reported that, despite phenotypic heterogeneity, genomic signatures of livers from patients display a proinflammatory phenotype. Here, we address the hypothesis that production of IFN-gamma is a key pathogenic mechanism of disease using a mouse model of rotavirus-induced biliary atresia. We found that rotavirus infection of neonatal mice has a unique tropism to bile duct cells, and it triggers a hepatobiliary inflammation by IFN-gamma-producing CD4(+) and CD8(+) lymphocytes. The inflammation is tissue specific, resulting in progressive jaundice, growth failure, and greater than 90% mortality due to obstruction of extrahepatic bile ducts. In this model, the genetic loss of IFN-gamma did not alter the onset of jaundice, but it remarkably suppressed the tissue-specific targeting of T lymphocytes and completely prevented the inflammatory and fibrosing obstruction of extrahepatic bile ducts. As a consequence, jaundice resolved, and long-term survival improved to greater than 80%. Notably, administration of recombinant IFN-gamma led to recurrence of bile duct obstruction following rotavirus infection of IFN-gamma-deficient mice. Thus, IFN-gamma-driven obstruction of bile ducts is a key pathogenic mechanism of disease and may constitute a therapeutic target to block disease progression in patients with biliary atresia.
| S-EPMC484981 | biostudies-literature
Project description:Biliary atresia (BA) is the leading indication for pediatric liver transplantation. Rhesus rotavirus (RRV) induced murine BA develops an obstructive cholangiopathy that mirrors the human disease. We have previously demonstrated the "SRL" motif on RRV's VP4 protein binds to heat shock cognate 70 protein (Hsc70) facilitating entry into cholangiocytes. In this study, we analyzed how binding to Hsc70 affects viral endocytosis, intracellular trafficking, and uniquely activates the signaling pathway that induces murine BA. Inhibition of clathrin- and dynamin-mediated endocytosis in cholangiocytes following infection demonstrated blocking dynamin decreased the infectivity of RRV whereas clathrin inhibition had no eaffect. Blocking early endosome trafficking resulted in decreased viral titers of RRV while late endosome inhibition had no effect. Following infection, p-NF-?B levels and TLR3 expression increased in cholangiocytes, leading to increased release of CXCL9 and CXCL10. Infected mice knocked out for TLR3 had decreased levels of CXLC9 and CXCL10, resulting in reduced NK cell numbers. Human BA patients experienced an increase in CXCL10 levels, suggesting this as a possible pathway leading to biliary obstruction. Viruses that utilize Hsc70 for cell entry exploit a chlathrin-independent pathway and traffic to the early recycling endosome uniquely activating NF-kB through TLR3, releasing leading to the release of CXCL9 and CXCL10, and inducing NK cell recruitment. These results define how the "SRL" peptide found on RRV's VP4 protein modulates viral trafficking, inducing the host response leading to bile duct obstruction.
2024-05-29 | GSE267721 | GEO