ArticleNature communications2022
Biliary NIK promotes ductular reaction and liver injury and fibrosis in mice.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 45 citations in OpenAlex.
- Precision inflammation targeting via myeloperoxidase mediated antioxidant melanin nanomedicines for chronic inflammation therapy.Nature communications · 2026Article
- miR-140-5p Inhibition alleviates LPS-induced cholangitis in rats and is associated with modulation of the NF-κB signaling pathway.Scientific reports · 2026Article
- Residual bile flow shapes PPARγ-mediated antifibrotic responses in experimental segmental cholestasis.Scientific reports · 2026Article
- Liver sinusoidal endothelial TGF-β signaling accelerates partial endothelial-mesenchymal transition and MASH through Notch.JHEP reports : innovation in hepatology · 2026Article
- Brown adipose tissue inactivation exacerbates alcohol-induced liver steatosis, inflammation, and fibrosis.American journal of physiology. Gastrointestinal and liver physiology · 2026Article
- Unveiling a novel macrophage-driven mechanism for obeticholic acid-induced liver injury in cholestatic: targeting NLRP12Cell biology and toxicology · 2026Article
- Key Experimental Therapeutics and Knowledge Gaps in Metabolic Dysfunction-Associated Steatohepatitis (MASH).Drug design, development and therapy · 2026Review
- Modulation of Inflammation-Driven Hepatocarcinogenesis: The Hepatic Immune Microenvironment, Gut-Liver Axis, and Neuroregulation.Journal of hepatocellular carcinoma · 2026Review
- Biliary NF-κB-Inducing Kinase Promotes Ductular Reaction, Inflammation, and Fibrosis and Impedes Liver Disease Resolution.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Dissecting the mechanisms of MASLD fibrosis in the era of single-cell and spatial omics.The Journal of clinical investigation · 2025Review
- Review
- Vitamin D supplementation ameliorates ductular reaction, liver inflammation and fibrosis in mice by upregulating TXNIP in ductular cells.Nature communications · 2025Article
- When getting reactive becomes the nORM: the emerging roles of proinflammatory cholangiokines.Gut · 2025Article
- Microenvironmental control of the ductular reaction: balancing repair and disease progression.Cell death & disease · 2025Review
- SOX9: a key transcriptional regulator in organ fibrosis.Frontiers in pharmacology · 2025Review
- Steatotic liver disease and cancer: from pathogenesis to therapeutic targets.eGastroenterology · 2025Review
- NIK Is a Mediator of Inflammation and Intimal Hyperplasia in Endothelial Denudation-Induced Vascular Injury.International journal of molecular sciences · 2024Article
- Bile Acids-Based Therapies for Primary Sclerosing Cholangitis: Current Landscape and Future Developments.Cells · 2024Review
- Hepatic Snai1 and Snai2 promote liver regeneration and suppress liver fibrosis in mice.Cell reports · 2024Article
- Review
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
Excessive cholangiocyte expansion (ductular reaction) promotes liver disease progression, but the underlying mechanism is poorly understood. Here we identify biliary NF-κB-inducing kinase (NIK) as a pivotal regulator of ductular reaction. NIK is known to activate the noncanonical IKKα/NF-κB2 pathway and regulate lymphoid tissue development. We find that cholangiocyte NIK is upregulated in mice with cholestasis induced by bile duct ligation (BDL), 5-diethoxycarbonyl-1,4-dihydrocollidine (DDC), or α-naphtyl-isothiocyanate (ANIT). DDC, ANIT, or BDL induces ductular reaction, liver injury, inflammation, and fibrosis in mice. Cholangiocyte-specific deletion of NIK, but not IKKα, blunts these pathological alterations. NIK inhibitor treatment similarly ameliorates DDC-induced ductular reaction, liver injury, and fibrosis. Biliary NIK directly increases cholangiocyte proliferation while suppressing cholangiocyte death, and it also promotes secretion of cholangiokines from cholangiocytes. Cholangiokines stimulate liver macrophages and hepatic stellate cells, augmenting liver inflammation and fibrosis. These results unveil a NIK/ductular reaction axis and a NIK/cholangiokine axis that promote liver disease progression.
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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.