ArticleHepatology (Baltimore, Md.)2016
The toxin biliatresone causes mouse extrahepatic cholangiocyte damage and fibrosis through decreased glutathione and SOX17.
Article in Hepatology (Baltimore, Md.), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers.
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70 citing papers in PubMed, 110 citations in OpenAlex.
- A phase 2 trial of short-term intravenous N-acetylcysteine in biliary atresia after Kasai portoenterostomy.Hepatology communications · 2025Trial
- The Dual Roles of Gut Microbiota in Biliary Atresia: Mechanisms, Biomarker Potential, and Therapeutic Implications.Microorganisms · 2026Review
- Human Organoids and Organ-on-Chip for Biotoxin Assessment: Applications, Best Practices, and a Translational Roadmap.Toxins · 2026Review
- Human biliary atresia extrahepatic cholangiocyte organoids express increased ER and oxidative stress, altered drug metabolism and cell polarity changes.Frontiers in bioengineering and biotechnology · 2026Article
- Next-Generation Hydrogels for Biliary Organoid Engineering.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Sound-controlled fluidic processor.Science advances · 2025Article
- Consensus classification of biliary complications after liver transplantation: guidelines from the BileducTx meeting.The British journal of surgery · 2025Article
- Biliary atresia: insights into mechanisms using a toxic model of the disease including Wnt and Hippo signaling pathways and microtubules.Pediatric research · 2025Article
- Organoids in biliary atresia.World journal of pediatric surgery · 2025Review
- Transcriptional analysis of murine biliary atresia identifies macrophage heterogeneity and subset-specific macrophage functions.Frontiers in immunology · 2025Article
- Microcystin-RR is a biliary toxin selective for neonatal extrahepatic cholangiocytes.JHEP reports : innovation in hepatology · 2025Article
- Generation of human induced pluripotent stem cell lines derived from patients of cystic biliary atresia.Human cell · 2024Article
- Oral N-acetylcysteine ameliorates liver fibrosis and enhances regenerative responses in Mdr2 knockout mice.Scientific reports · 2024Article
- Mechanism of biliary atresia caused by T follicular helper cells-induced immune injury.BMC pediatrics · 2024Article
- Biliary atresia.Nature reviews. Disease primers · 2024Review
- Impact of gallbladder hypoplasia on hilar hepatic ducts in biliary atresia.Communications medicine · 2024Article
- Progress in Biomarkers Related to Biliary Atresia.Journal of clinical and translational hepatology · 2024Review
- Article
- Glutathione: A Key Regulator of Extracellular Matrix and Cell Death in Intervertebral Disc Degeneration.Mediators of inflammation · 2024Review
- Article
10 more citing papers are in PubMed but not listed here.
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12 authors at 5 institutions in 3 countries.
Funding
Abstract
unlabelledBiliary atresia, the most common indication for pediatric liver transplantation, is a fibrotic disease of unknown etiology affecting the extrahepatic bile ducts of newborns. The recently described toxin biliatresone causes lumen obstruction in mouse cholangiocyte spheroids and represents a new model of biliary atresia. The goal of this study was to determine the cellular changes caused by biliatresone in mammalian cells that ultimately lead to biliary atresia and extrahepatic fibrosis. We treated mouse cholangiocytes in three-dimensional (3D) spheroid culture and neonatal extrahepatic duct explants with biliatresone and compounds that regulate glutathione (GSH). We examined the effects of biliatresone on SOX17 levels and determined the effects of Sox17 knockdown on cholangiocytes in 3D culture. We found that biliatresone caused disruption of cholangiocyte apical polarity and loss of monolayer integrity. Spheroids treated with biliatresone had increased permeability as shown by rhodamine efflux within 5 hours compared with untreated spheroids, which retained rhodamine for longer than 12 hours. Neonatal bile duct explants treated with the toxin showed lumen obstruction with increased subepithelial staining for α-smooth muscle actin and collagen, consistent with fibrosis. Biliatresone caused a rapid and transient decrease in GSH, which was both necessary and sufficient to mediate its effects in cholangiocyte spheroid and bile duct explant systems. It also caused a significant decrease in cholangiocyte levels of SOX17, and Sox17 knockdown in cholangiocyte spheroids mimicked the effects of biliatresone.
conclusionBiliatresone decreases GSH and SOX17 in mouse cholangiocytes. In 3D cell systems, this leads to cholangiocyte monolayer damage and increased permeability; in extrahepatic bile duct explants, it leads to disruption of the extrahepatic biliary tree and subepithelial fibrosis. This mechanism may be important in understanding human biliary atresia. (Hepatology 2016;64:880-893).
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