ArticleInflammation and regeneration2023
Atypical cholangiocytes derived from hepatocyte-cholangiocyte transdifferentiation mediated by COX-2: a kind of misguided liver regeneration.
Article in Inflammation and regeneration, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 9 citations in OpenAlex.
- Derepression of the epithelial transcription factor GRHL2 promotes direct hepatocyte-to-cholangiocyte transdifferentiation.PLoS biology · 2025Article
- Bioengineered Bile Duct for Liver Regenerative Medicine and Bile Duct Reconstruction.JGH open : an open access journal of gastroenterology and hepatology · 2025Review
- Review
- Inhibition of Cyclooxygenase-2 Upregulates the Nuclear Factor Erythroid 2-related Factor 2 Signaling Pathway to Mitigate Hepatocyte Ferroptosis in Chronic Liver Injury.Journal of clinical and translational hepatology · 2025Article
- Molecular mechanisms in liver repair and regeneration: from physiology to therapeutics.Signal transduction and targeted therapy · 2025Review
- Review
- Deconvolution analysis identified altered hepatic cell landscape in primary sclerosing cholangitis and primary biliary cholangitis.Frontiers in medicine · 2024Article
- Disruption of cholangiocyte-B cell crosstalk by blocking the CXCL12-CXCR4 axis alleviates liver fibrosis.Cellular and molecular life sciences : CMLS · 2023Article
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundHepatocyte-cholangiocyte transdifferentiation (HCT) is a potential origin of proliferating cholangiocytes in liver regeneration after chronic injury. This study aimed to determine HCT after chronic liver injury, verify the impacts of HCT on liver repair, and avoid harmful regeneration by understanding the mechanism.
methodsA thioacetamide (TAA)-induced liver injury model was established in wild-type (WT-TAA group) and COX-2 panknockout (KO-TAA group) mice. HCT was identified by costaining of hepatocyte and cholangiocyte markers in vivo and in isolated mouse hepatocytes in vitro. The biliary tract was injected with ink and visualized by whole liver optical clearing. Serum and liver bile acid (BA) concentrations were measured. Either a COX-2 selective inhibitor or a β-catenin pathway inhibitor was administered in vitro.
resultsIntrahepatic ductular reaction was associated with COX-2 upregulation in chronic liver injury. Immunofluorescence and RNA sequencing indicated that atypical cholangiocytes were characterized by an intermediate genetic phenotype between hepatocytes and cholangiocytes and might be derived from hepatocytes. The structure of the biliary system was impaired, and BA metabolism was dysregulated by HCT, which was mediated by the TGF-β/β-catenin signaling pathway. Genetic deletion or pharmaceutical inhibition of COX-2 significantly reduced HCT in vivo. The COX-2 selective inhibitor etoricoxib suppressed HCT through the TGF-β-TGFBR1-β-catenin pathway in vitro.
conclusionsAtypical cholangiocytes can be derived from HCT, which forms a secondary strike by maldevelopment of the bile drainage system and BA homeostasis disequilibrium during chronic liver injury. Inhibition of COX-2 could ameliorate HCT through the COX-2-TGF-β-TGFBR1-β-catenin pathway and improve liver function.
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