ArticleThe American journal of pathology2007
A new xenobiotic-induced mouse model of sclerosing cholangitis and biliary fibrosis.
Article in The American journal of pathology, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 175 papers, 1 of them a synthesis that pooled it.
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Who cites it
175 citing papers in PubMed, 1 synthesis or guideline pooled it, 372 citations in OpenAlex.
- Pooled it
- Gd-EOB-DTPA-enhanced MRI in the diagnosis of intrahepatic cholestasis in mice: an experimental study.BMC medical imaging · 2026Article
- Article
- Cholangiocyte biology in primary sclerosing cholangitis and other cholangiopathies: pathogenesis, clinical insights, and experimental tools.Physiological reviews · 2026Review
- Spatial hepatology: Decoding liver zonation for metabolic and regenerative therapeutics (Review).International journal of molecular medicine · 2026Review
- Hepatocyte TEAD1 drives epithelial-stromal remodeling during cholestatic liver injury.bioRxiv : the preprint server for biology · 2026Article
- E2F2 transcription factor promotes a cholestatic MASH phenotype by regulating hepatobiliary metabolism through miR-34a-5p.Hepatology (Baltimore, Md.) · 2026Article
- FXR-YAP signalling maintains biliary epithelial cell identity and preserves liver homeostasis.Nature metabolism · 2026Article
- Anti-endoglin monoclonal antibody TRC105 prevents the increase of liver inflammatory biomarkers in a mouse model of cholestasis.Cellular and molecular life sciences : CMLS · 2026Article
- An immunobiliary single-cell atlas resolves crosstalk between type 2 conventional dendritic cells and γδ T cells in cholangitis.Nature communications · 2026Article
- Moderate increase of MET in hepatocytes protects against cholestatic liver injury by promoting an effective antioxidant response.The FEBS journal · 2026Article
- Dysbiosis in the Gut-Liver Axis Is Associated With Low Bone Mass During Murine Cholestasis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- A spatially localised cryoinjury protocol to study liver regeneration in zebrafish.STAR protocols · 2026Article
- Loss of β-catenin in cholangiocytes promotes hepatocyte reprogramming and vascular remodeling during murine cholestasis.Cell communication and signaling : CCS · 2026Article
- Dietary Lauric Acid Suppresses Inflammation, Cholestasis, Hepatocyte Injury, and Senescence in 3,5-Diethoxycarbonyl-1,4-Dihydrocollidine-induced Inflammatory Cholangiopathy.Cellular and molecular gastroenterology and hepatology · 2026Article
- Article
- Animal Models of Porphyria with Hepatic Involvement.Seminars in liver disease · 2025Review
- EGFR activation in cholangiocytes promotes extrahepatic bile duct regeneration after injury.Hepatology communications · 2025Article
- Bile acids engage the SIPR-STAT3 signaling axis to modulate regulatory T cell responses in fibrosing cholangiopathies.Journal of hepatology · 2025Article
- Dynamic cholangiocyte responses in a murine model of reversible cholestasis: macrophage remodeling and NF-Y-mediated TGFβ1 expression.American journal of physiology. Gastrointestinal and liver physiology · 2025Article
115 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Xenobiotics and drugs may lead to cholangiopathies and biliary fibrosis, but the underlying mechanisms are largely unknown. Therefore, we aimed to characterize the cause and consequences of hepatobiliary injury and biliary fibrosis in 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC)-fed mice as a novel model of xenobiotic-induced cholangiopathy. Liver morphology, markers of inflammation, cell proliferation, fibrosis, bile formation, biliary porphyrin secretion, and hepatobiliary transporter expression were studied longitudinally in DDC- and control diet-fed Swiss albino mice. DDC feeding led to increased biliary porphyrin secretion and induction of vascular cell adhesion molecule, osteopontin, and tumor necrosis factor-alpha expression in bile duct epithelial cells. This was associated with a pronounced pericholangitis with a significantly increased number of CD11b-positive cells, ductular reaction, and activation of periductal myofibroblasts, leading to large duct disease and a biliary type of liver fibrosis. After 4 weeks, we constantly observed intraductal porphyrin pigment plugs. Glutathione and phospholipid excretion significantly decreased over time. Expression of Ntcp, Oatp4, and Mrp2 was significantly reduced, whereas Bsep expression remained unchanged and adaptive Mrp3 and Mrp4 expression was significantly induced. We demonstrate that DDC feeding in mice leads to i) a reactive phenotype of cholangiocytes and bile duct injury, ii) pericholangitis, periductal fibrosis, ductular reaction, and consequently portal-portal bridging, iii) down-regulation of Mrp2 and impaired glutathione excretion, and iv) segmental bile duct obstruction. This model may be valuable to investigate the mechanisms of xenobiotic-induced chronic cholangiopathies and its sequels including biliary fibrosis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.