ArticleHepatology (Baltimore, Md.)2020
Immune-Responsive Gene 1/Itaconate Activates Nuclear Factor Erythroid 2-Related Factor 2 in Hepatocytes to Protect Against Liver Ischemia-Reperfusion Injury.
Article in Hepatology (Baltimore, Md.), 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 120 papers.
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Who cites it
120 citing papers in PubMed, 232 citations in OpenAlex.
- 4-Octyl Itaconate Attenuates Age-Induced Parotid Gland Dysfunction Through the Suppression of Fibrosis and Lipid Deposition by AMPKα/PPARα and the Inhibition of Oxidative Stress via the AMPKα/Nrf2 Signaling Pathway.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Dynamic metabolic programming of monocyte-derived cells defines immunity in CNS disease.Brain : a journal of neurology · 2026Review
- Itaconate metabolism in regulated cell death.Molecular and cellular biochemistry · 2026Review
- Itaconate and its derivatives in human health and diseases.Signal transduction and targeted therapy · 2026Review
- Four-Octyl Itaconate Alleviates Enterococcus faecalis-Induced Apical Periodontitis by Inhibiting Macrophage M1 Polarisation.International endodontic journal · 2026Article
- Obesity suppresses neutrophil-dependent itaconate signaling promoting ferroptosis in acute pancreatitis.Redox biology · 2026Article
- Rutin attenuates liver fibrosis via the IRG1-itaconate-Nrf2 axis.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Article
- Inhibition of Toxoplasma gondii proliferation by dimethyl itaconate: Evidence from in vitro and in vivo studies.PLoS neglected tropical diseases · 2026Article
- ACOD1 deficiency promotes DDX1 methylation-mediated mitochondrial dysfunction and dermal papilla cell senescence in androgenetic alopecia.BMC medicine · 2026Article
- Protective role of IRG1/itaconate in acute myocardial injury: association with NLRP3 inflammasome and oxidative stress.Scientific reports · 2026Article
- TLR4 maintains Treg-mediated protection against adverse outcomes in a model of hepatic surgical stress.The Journal of clinical investigation · 2026Article
- Neurotrophic Factors: Emerging Biology and Therapeutic Applications for Cardiovascular Diseases.Metabolites · 2026Review
- Metabolic control of neuroinflammation: focus on itaconate and its derivatives in CNS disorders.Frontiers in immunology · 2026Review
- Macrophage polarization in ischemia-reperfusion injury: from molecular mechanisms to therapeutic strategies.Frontiers in immunology · 2026Review
- IRG1-itaconate axis in immunometabolism: mechanistic roles and therapeutic potential in inflammatory diseases.Frontiers in immunology · 2026Review
- Article
- Dimethyl itaconate suppresses dendritic cell and CD8BMC medicine · 2025Article
- 4-octyl Itaconate Attenuates Acute Pancreatitis and Associated Lung Injury by Suppressing Ferroptosis in Mice.Inflammation · 2025Article
- Reprogramming immunity with itaconate: metabolic mechanisms and therapeutic perspectives.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025Review
- Elevated GFI1 in Alveolar Macrophages Suppresses ACOD1 Expression and Exacerbates Lipopolysaccharide-Induced Lung Injury in Obesity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
60 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
Abstract
BACKGROUND AND
aimsItaconate, a metabolite of the tricarboxylic acid cycle, plays anti-inflammatory roles in macrophages during endotoxemia. The mechanisms underlying its anti-inflammatory roles have been shown to be mediated by the modulation of oxidative stress, an important mechanism of hepatic ischemia-reperfusion (I/R) injury. However, the role of itaconate in liver I/R injury is unknown. APPROACH AND
resultsWe found that deletion of immune-responsive gene 1 (IRG1), encoding for the enzyme producing itaconate, exacerbated liver injury and systemic inflammation. Furthermore, bone marrow adoptive transfer experiments indicated that deletion of IRG1 in both hematopoietic and nonhematopoietic compartments contributes to the protection mediated by IRG1 after I/R. Interestingly, the expression of IRG1 was up-regulated in hepatocytes after I/R and hypoxia/reoxygenation-induced oxidative stress. Modulation of the IRG1 expression levels in hepatocytes regulated hepatocyte cell death. Importantly, addition of 4-octyl itaconate significantly improved liver injury and hepatocyte cell death after I/R. Furthermore, our data indicated that nuclear factor erythroid 2-related factor 2 (Nrf2) is required for the protective effect of IRG1 on mouse and human hepatocytes against oxidative stress-induced injury. Our studies document the important role of IRG1 in the acute setting of sterile injury induced by I/R. Specifically, we provide evidence that the IRG1/itaconate pathway activates Nrf2-mediated antioxidative response in hepatocytes to protect liver from I/R injury.
conclusionsOur data expand on the importance of IRG1/itaconate in nonimmune cells and identify itaconate as a potential therapeutic strategy for this unfavorable postsurgical complication.
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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.