ArticleHepatology (Baltimore, Md.)2012
Receptor activator of nuclear factor-κB ligand (RANKL) protects against hepatic ischemia/reperfusion injury in mice.
Article in Hepatology (Baltimore, Md.), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 57 citations in OpenAlex.
- Article
- MyD88 Inhibition Ameliorates Diabetes-Induced Hepatic Inflammation and Gluconeogenesis Through Adipose IL-10 Induction.International journal of molecular sciences · 2026Article
- Exosomal miR-216a-5p targeting TLR-4 alleviates liver ischemia-reperfusion injury by regulating M2 macrophage polarization and neutrophil inflammation.Annals of medicine · 2025Article
- Incomplete elimination of viral genomes is associated with chronic inflammation in nonhuman primate livers after AAV-mediated gene transfer.Gene therapy · 2025Article
- Ischemia-reperfusion injury: molecular mechanisms and therapeutic targets.Signal transduction and targeted therapy · 2024Review
- Modulation of the hepatic RANK-RANKL-OPG axis by combined C5 and CD14 inhibition in a long-term polytrauma model.Frontiers in immunology · 2024Article
- Article
- Delayed denervation-induced muscle atrophy inFrontiers in physiology · 2023Article
- Inflammatory response to the ischaemia-reperfusion insult in the liver after major tissue trauma.European journal of trauma and emergency surgery : official publication of the European Trauma Society · 2022Review
- Progress and Prospects of Non-Canonical NF-κB Signaling Pathway in the Regulation of Liver Diseases.Molecules (Basel, Switzerland) · 2022Review
- The effects of hepatic ischemia/reperfusion injury on postoperative cognitive function in aged rats.Archives of medical science : AMS · 2022Article
- [The pathogenesis of ischemic hepatitis].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2021Article
- NR4A1 knockdown confers hepatoprotection against ischaemia-reperfusion injury by suppressing TGFβ1 via inhibition of CYR61/NF-κB in mouse hepatocytes.Journal of cellular and molecular medicine · 2021Article
- Article
- Circular RNA Microarray Analyses in Hepatic Ischemia-Reperfusion Injury With Ischemic Preconditioning Prevention.Frontiers in medicine · 2021Article
- An adverse outcome pathway for immune-mediated and allergic hepatitis: a case study with the NSAID diclofenac.Archives of toxicology · 2020Article
- Osteoprotegerin is More than a Possible Serum Marker in Liver Fibrosis: A Study into its Function in Human and Murine Liver.Pharmaceutics · 2020Article
- Six-Transmembrane Epithelial Antigen of the Prostate 3 Deficiency in Hepatocytes Protects the Liver Against Ischemia-Reperfusion Injury by Suppressing Transforming Growth Factor-β-Activated Kinase 1.Hepatology (Baltimore, Md.) · 2020Article
- Transcriptomic Analysis of Rat Macrophages.Frontiers in immunology · 2020Article
- [Toll-like receptor 4 in liver ischemia-reperfusion injury].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2019Review
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8 authors at 1 institution in 1 country.
Funding
Abstract
unlabelledThe transcription factor nuclear factor kappaB (NF-κB) plays diverse roles in the acute injury response to hepatic ischemia/reperfusion (I/R). Activation of NF-κB in Kupffer cells promotes inflammation through cytokine expression, whereas activation in hepatocytes may be cell protective. The interaction of receptor activator of NF-κB (RANK) and its ligand (RANKL) promotes NF-κB activation; however, this ligand-receptor system has not been studied in acute liver injury. In the current study, we sought to determine if RANK and RANKL were important in the hepatic response to I/R. Mice were subjected to partial hepatic ischemia followed by reperfusion. In some experiments, mice received recombinant RANKL or neutralizing antibodies to RANKL 1 hour prior to surgery or at reperfusion to assess the role of RANK/RANKL signaling during I/R injury. RANK was constitutively expressed in the liver and was not altered by I/R. RANK was strongly expressed in hepatocytes and very weakly expressed in Kupffer cells. Serum RANKL concentrations increased after I/R and peaked 4 hours after reperfusion. Serum levels of osteoprotegerin (OPG), a decoy receptor for RANKL, steadily increased over the 8-hour period of reperfusion. Treatment with RANKL, before ischemia or at reperfusion, increased hepatocyte NF-κB activation and significantly reduced liver injury. These beneficial effects occurred without any effect on cytokine expression or liver inflammation. Treatment with anti-RANKL antibodies had no effect on liver I/R injury.
conclusionDuring the course of injury, endogenous OPG appears to suppress the effects of RANKL. However, exogenous administration of RANKL, given either prophylactically or postinjury, reduces liver injury in a manner associated with increased hepatocyte NF-κB activation. The data suggest that RANK/RANKL may be a viable therapeutic target in acute liver injury.
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