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Comprehensive gene expression profile of mouse extrahepatic bileducts and gallbladder during a mouse model of biliary atresia.

ABSTRACT: 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE41594 | GEO | 2013/10/15

SECONDARY ACCESSION(S): PRJNA177631

REPOSITORIES: GEO

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Comprehensive gene expression profile of mouse extrahepatic bileducts and gallbladder during a mouse model of biliary atresia.

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

Taqman Low Density Arrays (TLDA) based microRNAs expression profile of mouse extrahepatic bileducts and gallbladders during a mouse model of biliary atresia.

2013-10-15 | GSE41593 | GEO

Taqman Low Density Arrays (TLDA) based microRNAs expression profile of mouse extrahepatic bileducts and gallbladders during a mouse model of biliary atresia.

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

Comprehensive gene expression profile of extrahepatic bile ducts in mice with experimental biliary atresia

2013-06-01 | GSE46967 | GEO

Comprehensive gene expression profile of extrahepatic bile ducts in mice with experimental biliary atresia

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

Extrahepatic cholangiocyte cilia are abnormal in biliary atresia.

Project description:OBJECTIVES:Biliary atresia (BA) is a rapidly progressive form of biliary fibrosis affecting neonates. We previously reported that primary cilia on the intrahepatic cholangiocytes of patients with both syndromic and nonsyndromic BA were structurally abnormal. Our objective was to determine whether extrahepatic cholangiocytes in human biliary atresia, intrahepatic and extrahepatic cholangiocytes of rhesus rotavirus (RRV)-infected neonatal mice, and RRV-infected primary neonatal extrahepatic cholangiocytes also demonstrate ciliary abnormalities. METHODS:The livers of neonatal BALB/c mice injected with RRV that developed jaundice, human extrahepatic bile duct samples obtained at time of hepatoportoenterostomy, and RRV-infected primary neonatal cholangiocytes were stained with antibodies against acetylated ? tubulin to identify primary cilia. RESULTS:Extrahepatic cholangiocytes from RRV-treated mice demonstrated minimal loss of primary cilia at day 3 but almost complete loss at day 8 and partial loss at day 12. No changes were seen in mouse intrahepatic bile ducts at any of the time points. In the human BA samples, primary cilia were almost completely absent from extrahepatic duct cholangiocytes. There were, however, abundant cilia in the peribiliary glands adjacent to extrahepatic ducts in the BA sample. Cilia in RRV-infected primary neonatal cholangiocytes were significantly decreased compared with controls. CONCLUSIONS:Primary cilia are selectively lost from neonatal extrahepatic but not intrahepatic cholangiocytes after RRV infection in BALB/c mice. The cilia are also decreased in RRV-infected primary cholangiocytes and the extrahepatic ducts from human patients with BA. This suggests that ciliary abnormalities are part of the pathophysiology of BA.

| S-EPMC3696479 | biostudies-literature

Prominin-1 promotes restitution of the murine extrahepatic biliary luminal epithelium following cholestatic liver injury

Project description:Restitution of the extrahepatic biliary luminal epithelium in cholangiopathies is poorly understood. Prominin-1 (Prom1) is a key component of epithelial ciliary body of stem/progenitor cells. Given that intrahepatic Prom1-expressing progenitor cells undergo cholangiocyte differentiation, we hypothesized that Prom1 may promote restitution of the extrahepatic bile duct (EHBD) epithelium following injury. Utilizing various murine biliary injury models, we identified Prom1-expressing cells in the peribiliary glands (PBGs) of the EHBD. These Prom1-expressing cells are progenitor cells which give rise to cholangiocytes as part of the normal maintenance of the EHBD epithelium. Following injury, these cells proliferate significantly more rapidly to re-populate the biliary luminal epithelium. Null mutation of Prom1 leads to significantly more than ten-fold dilated PBGs following rhesus rotavirus-mediated biliary injury. Cultured organoids derived from Prom1 knockout mice are comprised of biliary progenitor cells with altered apical-basal cellular polarity, significantly fewer and shorter cilia, and decreased organoid proliferation dynamics consistent with impaired cell motility. We, therefore, conclude that Prom1 is involved in biliary epithelial restitution following biliary injury in part through its role in supporting cell polarity.

2022-12-05 | GSE220054 | GEO

The Utility of Gallbladder Absence on Ultrasound for Children With Biliary Atresia.

Project description:Background: Biliary Atresia (BA) is congenital condition, where infant intra- and extrahepatic bile ducts become obliterated, leading to cholestasis, and cirrhosis if untreated. This study aims to assess the predictive measure of absent gallbladder on ultrasounds (US) performed in infants with cholestasis for diagnosing BA. Method: After Institutional Review Board approval, retrospective chart reviews of 61 infants with cholestasis found 43 (70.5%) were diagnosed with BA. A pediatric radiologist provided interpretations of all ultrasounds in a blinded fashion. Statistical analysis was used to assess the utility of absence of gallbladder on US in predicting BA, confirmed intraoperatively. Results: Absent gallbladder on US predicts absent gallbladder with 77% accuracy, 92% sensitivity, 73% specificity, PPV 43%, and NPV 97% (P < 0.001, Fisher exact test). To diagnose BA, absent gallbladder on US has 66% accuracy, 53% sensitivity, 94% specificity, 96% PPV, and 46% NPV (P < 0.001, Fisher exact test). Conclusion: Sonographic gallbladder absence has high specificity and PPV, indicating utility for BA diagnosis; however, it is not useful for ruling out BA given its low sensitivity.

| S-EPMC8275825 | biostudies-literature

Helicobacter species in cancers of the gallbladder and extrahepatic biliary tract.

Project description:Helicobacter species have been found in human bile and biliary tract (BT) tissue and are suspected to cause BT diseases, including gallbladder and extrahepatic cancers, collectively referred to in this work as BT cancers. We conducted a literature review of the epidemiological evidence linking the presence of Helicobacter species in bile or BT biopsies to BT cancers and benign diseases. Reports showed great variability with respect to study methods. Nine studies of BT cancers were identified, all with 30 or fewer BT cancers; eight included cancer-free control subjects and used polymerase chain reaction (PCR) as a means of Helicobacter species detection. In four of these studies, Helicobacter species were detected in patients with BT cancer significantly more frequently than in controls, at least when controls without BT diseases were used. In two studies, no Helicobacter species were detected in either cases or controls. Helicobacter species were also often detected in benign BT diseases such as gallstone disease or chronic cholecystitis. As our current knowledge relies on a few small studies that showed substantial differences, larger studies and more standardised protocols for detecting DNA and antibodies against Helicobacter species are needed to investigate a potential association with BT cancer.

| S-EPMC2634699 | biostudies-other

Gallbladder wall abnormality in biliary atresia of mouse Sox17+/- neonates and human infants.

Project description:Biliary atresia (BA) is characterized by the inflammation and obstruction of the extrahepatic bile ducts (EHBDs) in newborn infants. SOX17 is a master regulator of fetal EHBD formation. In mouse Sox17+/- BA models, SOX17 reduction causes cell-autonomous epithelial shedding together with the ectopic appearance of SOX9-positive cystic duct-like epithelia in the gallbladder walls, resulting in BA-like symptoms during the perinatal period. However, the similarities with human BA gallbladders are still unclear. In the present study, we conducted phenotypic analysis of Sox17+/- BA neonate mice, in order to compare with the gallbladder wall phenotype of human BA infants. The most characteristic phenotype of the Sox17+/- BA gallbladders is the ectopic appearance of SOX9-positive peribiliary glands (PBGs), so-called pseudopyloric glands (PPGs). Next, we examined SOX17/SOX9 expression profiles of human gallbladders in 13 BA infants. Among them, five BA cases showed a loss or drastic reduction of SOX17-positive signals throughout the whole region of gallbladder epithelia (SOX17-low group). Even in the remaining eight gallbladders (SOX17-high group), the epithelial cells near the decidual sites were frequently reduced in the SOX17-positive signal intensity. Most interestingly, the most characteristic phenotype of human BA gallbladders is the increased density of PBG/PPG-like glands in the gallbladder body, especially near the epithelial decidual site, indicating that PBG/PPG formation is a common phenotype between human BA and mouse Sox17+/- BA gallbladders. These findings provide the first evidence of the potential contribution of SOX17 reduction and PBG/PPG formation to the early pathogenesis of human BA gallbladders.This article has an associated First Person interview with the joint first authors of the paper.

| S-EPMC7132780 | biostudies-literature

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