ArticleGut2025
Reactive cholangiocyte-derived ORM2 drives a pathogenic modulation of the injured biliary niche through macrophage reprogramming.
Article in Gut, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed.
- Reverse bioengineering of the liver: developmental principles for next-generation liver-on-a-chip systems.Communications biology · 2026Review
- Review
- Hepatokine ORM2 suppresses pathological ferritinophagy to prevent acute tissue injury.Cell death & disease · 2026Article
- Hepatocyte Mettl3 Deficiency Drives Primary Sclerosing Cholangitis and Liver Fibrosis via Cholangiocyte-Macrophage Crosstalk.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- The KDM6B/SLC10A2 Axis Suppresses MDSCs Recruitment via ERK/AP-1 Signaling in Colorectal Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Unified platform for multiplex immunofluorescence across liver tissues and engineered models.eGastroenterology · 2026Article
- Key Experimental Therapeutics and Knowledge Gaps in Metabolic Dysfunction-Associated Steatohepatitis (MASH).Drug design, development and therapy · 2026Review
- Conserved Ductular Reaction Mechanisms in Biliary Atresia and Primary Sclerosing Cholangitis Derived From Single-Cell and Spatial Transcriptomics.Cellular and molecular gastroenterology and hepatology · 2026Review
- Neutrophil and macrophage zonation in liver disease: from spatiotemporal dynamics to advanced computational analysis.Frontiers in immunology · 2026Review
- Integrated transcriptomics-metabolomics analysis reveals biomarkers and metabolic dysregulation characteristics of parenteral nutrition-associated liver disease.Frontiers in nutrition · 2026Article
- Orosomucoid 2 (ORM2) in type 2 diabetes and coronary artery disease: a potential link between insulin resistance and vascular inflammation.Frontiers in cardiovascular medicine · 2026Review
- Inflammation and immunity in liver homeostasis and disease: a nexus of hepatocytes, nonparenchymal cells and immune cells.Cellular & molecular immunology · 2025Review
- Review
- When getting reactive becomes the nORM: the emerging roles of proinflammatory cholangiokines.Gut · 2025Article
- Engineering liver disease models in vitro: emerging trends and innovations.eGastroenterology · 2025Review
Corrections and comments
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Authors and funding
14 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundInjured or reactive biliary epithelial cells participate in most chronic liver injuries in a process referred to as ductular reaction, which involves multicellular interactions with marked local infiltration of macrophages and fibrogenic cell activation. The direct roles of biliary epithelial cells in shaping their cellular niche remain unknown.
objectiveWe aimed at investigating the effects of biliary epithelial cell-derived acute phase response protein orosomucoid 2 (ORM2) in shaping monocyte/macrophage response to liver injury.
designTranscriptome data sets from human and mouse livers were used, results were confirmed with multiplex immunofluorescence. A multicellular biliary-niche-on-a-chip derived from primary liver and blood cells (wild-type,
resultsOur transcriptome data set and multiplex immunofluorescence analyses indicated a previously unrecognised involvement of the acute phase response protein ORM2 in ductular reactions in both human and mouse livers. ORM2 gene expression was increased in biliatresone-challenged, bile acid-challenged and acetaminophen-challenged cholangiocytes. Cholangiocyte-derived ORM2 induced unique transcriptome changes and functional adaptation of liver macrophages. ORM2-activated macrophages exacerbated cholangiocyte cell stress and
conclusionThis study reveals a paracrine communication circuit during ductular reaction, in which reactive cholangiocyte-derived ORM2 reprogrammes liver macrophages, participating in a pathogenic remodelling of the immune biliary niche.
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