ArticleJournal of hepatology2023
A fetal wound healing program after intrauterine bile duct injury may contribute to biliary atresia.
Article in Journal of hepatology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 19 citations in OpenAlex.
- The instructive scar - the dynamic role of extracellular matrix in biliary pathophysiology.Disease models & mechanisms · 2026Review
- Analytical Assessment of Hyaluronan and Its Heavy Chain Modification with Solid-State Nanopore Sensors.Annual review of analytical chemistry (Palo Alto, Calif.) · 2026Review
- Understanding sub-cellular mechanochemical correlations of the neonatal extrahepatic bile duct extracellular matrix by atomic force microscope-Infrared spectroscopy.Analytica chimica acta · 2026Article
- Research progress of blood-brain barrier penetrating and brain diseases therapy by natural biopolymer - based nanomedicine delivery systems.Materials today. Bio · 2026Review
- Upregulated beta-defensin-1 in murine and human biliary atresia associates with human native liver survival.Scientific reports · 2026Article
- Approaching Scarless Wound Healing: From Passive Anti-Fibrotic to Proactive and Programmable Pro-Regenerative Strategies.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- The bile acid-gut microbiota-vitamin D axis: new insights into biliary atresia.Frontiers in cellular and infection microbiology · 2026Review
- Integrated transcriptomic and co-expression network analysis identifiesTranslational pediatrics · 2025Article
- IgG4-Related Cholangitis.Seminars in liver disease · 2025Review
- Microcystin-RR is a biliary toxin selective for neonatal extrahepatic cholangiocytes.JHEP reports : innovation in hepatology · 2025Article
- Transcriptional analysis of murine biliary atresia identifies macrophage heterogeneity and subset-specific macrophage functions.Frontiers in immunology · 2025Article
- Article
- Genetic background and biliary atresia.World journal of pediatric surgery · 2025Review
- Biliary atresia susceptibility gene EFEMP1 regulates extrahepatic bile duct elastic fiber formation and mechanics.JHEP reports : innovation in hepatology · 2025Article
- Silencing of maternally expressed RNAs in Dlk1-Dio3 domain causes fatal vascular injury in the fetal liver.Cellular and molecular life sciences : CMLS · 2024Article
- Biliary atresia.Nature reviews. Disease primers · 2024Review
- Targeted Analysis of the Size Distribution of Heavy Chain-Modified Hyaluronan with Solid-State Nanopores.Analytical chemistry · 2024Article
- Article
- In Utero Extrahepatic Bile Duct Damage and Repair: Implications for Biliary Atresia.Pediatric and developmental pathology : the official journal of the Society for Pediatric Pathology and the Paediatric Pathology SocietyReview
- High-fidelity and iterative affinity extraction of hyaluronan.Proteoglycan researchArticle
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Authors and funding
21 authors at 6 institutions in 4 countries.
Funding
Abstract
BACKGROUND &
aimsBiliary atresia (BA) is an obstructive cholangiopathy that initially affects the extrahepatic bile ducts (EHBDs) of neonates. The etiology is uncertain, but evidence points to a prenatal cause. Fetal tissues have increased levels of hyaluronic acid (HA), which plays an integral role in fetal wound healing. The objective of this study was to determine whether a program of fetal wound healing is part of the response to fetal EHBD injury.
methodsMouse, rat, sheep, and human EHBD samples were studied at different developmental time points. Models included a fetal sheep model of prenatal hypoxia, human BA EHBD remnants and liver samples taken at the time of the Kasai procedure, EHBDs isolated from neonatal rats and mice, and spheroids and other models generated from primary neonatal mouse cholangiocytes.
resultsA wide layer of high molecular weight HA encircling the lumen was characteristic of the normal perinatal but not adult EHBD. This layer, which was surrounded by collagen, expanded in injured ducts in parallel with extensive peribiliary gland hyperplasia, increased mucus production and elevated serum bilirubin levels. BA EHBD remnants similarly showed increased HA centered around ductular structures compared with age-appropriate controls. High molecular weight HA typical of the fetal/neonatal ducts caused increased cholangiocyte spheroid growth, whereas low molecular weight HA induced abnormal epithelial morphology; low molecular weight HA caused matrix swelling in a bile duct-on-a-chip device.
conclusionThe fetal/neonatal EHBD, including in human EHBD remnants from Kasai surgeries, demonstrated an injury response with prolonged high levels of HA typical of fetal wound healing. The expanded peri-luminal HA layer may swell and lead to elevated bilirubin levels and obstruction of the EHBD. IMPACT AND IMPLICATIONS: Biliary atresia is a pediatric cholangiopathy associated with high morbidity and mortality rates; although multiple etiologies have been proposed, the fetal response to bile duct damage is largely unknown. This study explores the fetal pathogenesis after extrahepatic bile duct damage, thereby opening a completely new avenue to study therapeutic targets in the context of biliary atresia.
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