ArticleHepatology (Baltimore, Md.)2014
Mouse hepatocyte overexpression of NF-κB-inducing kinase (NIK) triggers fatal macrophage-dependent liver injury and fibrosis.
Article in Hepatology (Baltimore, Md.), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.
What it found
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Who cites it
60 citing papers in PubMed, 94 citations in OpenAlex.
- The NF-κB Signalling Pathway: Mechanisms, Consequences and Therapeutic Targets.Journal of cellular and molecular medicine · 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
- METTL14-Induced MAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Neuronal injury and hepatotoxicity: astrocytes and stellate cells convergence and their role in tissue repair.Frontiers in neuroscience · 2025Review
- Chlorogenic Acid Ameliorates CClAnti-cancer agents in medicinal chemistry · 2025Article
- Potential therapeutic strategies for MASH: from preclinical to clinical development.Life metabolism · 2024Review
- Mitigating Acetaminophen-Induced Kidney Injury: The Protective Role of Grape Seed and Peanut Skin Extracts through the iNOS/CYP2E1 Pathway.ACS omega · 2024Article
- Stem cell-derived exosomes as a potential therapy for schistosomal hepatic fibrosis in experimental animals.Pathogens and global health · 2024Article
- Endotoxin Inflammatory Action on Cells by Dysregulated-Immunological-Barrier-Linked ROS-Apoptosis Mechanisms in Gut-Liver Axis.International journal of molecular sciences · 2024Article
- Correlation between SDF-1α, CD34 positive hematopoietic stem cells and CXCR4 expression with liver fibrosis in CCl4 rat model.BMC gastroenterology · 2023Article
- Notch-mediated hepatocyte MCP-1 secretion causes liver fibrosis.JCI insight · 2023Article
- Hepatic neddylation deficiency triggers fatal liver injury via inducing NF-κB-inducing kinase in mice.Nature communications · 2022Article
- Biliary NIK promotes ductular reaction and liver injury and fibrosis in mice.Nature communications · 2022Article
- Progress and Prospects of Non-Canonical NF-κB Signaling Pathway in the Regulation of Liver Diseases.Molecules (Basel, Switzerland) · 2022Review
- KRT17 Promotes the Activation of HSCs via EMT in Liver Fibrosis.Journal of clinical and translational hepatology · 2022Article
- Review
- Roles of IκB kinases and TANK-binding kinase 1 in hepatic lipid metabolism and nonalcoholic fatty liver disease.Experimental & molecular medicine · 2021Review
- Extra- and Intra-Cellular Mechanisms of Hepatic Stellate Cell Activation.Biomedicines · 2021Review
- Role of NF-κB in Ageing and Age-Related Diseases: Lessons from Genetically Modified Mouse Models.Cells · 2021Review
- Pharmacological inhibition of NF-κB-inducing kinase (NIK) with small molecules for the treatment of human diseases.RSC medicinal chemistry · 2021Review
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
unlabelledDamaged, necrotic, or apoptotic hepatocytes release damage-associated molecular patterns that initiate sterile inflammation, and liver inflammation drives liver injury and fibrosis. Here we identified hepatic nuclear factor kappa B (NF-κB)-inducing kinase (NIK), a Ser/Thr kinase, as a novel trigger of fatal liver inflammation. NIK is activated by a broad spectrum of stimuli. It was up-regulated in injured livers in both mice and humans. In primary mouse hepatocytes, NIK overexpression stimulated, independently of cell injury and death, release of numerous chemokines and cytokines that activated bone marrow-derived macrophages (BMDMs). BMDMs in turn secreted proapoptotic molecules that stimulated hepatocyte apoptosis. Hepatocyte-specific expression of the NIK transgene triggered massive liver inflammation, oxidative stress, hepatocyte apoptosis, and liver fibrosis, leading to weight loss, hypoglycemia, and death. Depletion of Kupffer cells/macrophages reversed NIK-induced liver destruction and death.
conclusionthe hepatocyte NIK-liver immune cell axis promotes liver inflammation, injury, and fibrosis, thus driving 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.