ArticleJournal of hepatology2017
Macrophage heme oxygenase-1-SIRT1-p53 axis regulates sterile inflammation in liver ischemia-reperfusion injury.
Article in Journal of hepatology, 2017. 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, 206 citations in OpenAlex.
- Daikenchuto and Processed Ginger Alleviate Liver Ischemia-Reperfusion Injury by Enhancing Anti-Inflammatory Effects and HO-1 Production.JGH open : an open access journal of gastroenterology and hepatology · 2026Article
- SIRT1 in Neurodegenerative Diseases: Molecular Mechanisms, Disease Relevance, and Therapeutic Potential.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Review
- Arrb2 in hepatocytes promotes M2 macrophage polarization, ameliorates hepatic ischemia-reperfusion injury through upregulating metabolite 6-ketoLCA.Hepatology communications · 2026Article
- Ubc9-mediated SUMOylation of Ninj1 alleviates inflammatory responses in hepatic ischaemia/reperfusion injury.Clinical and translational medicine · 2026Article
- Chaperone-Mediated Autophagic Degradation of USP9X in Macrophages Exacerbates Postmyocardial Infarction Inflammation and Cardiac Dysfunction.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Substantially Altered Local and Systemic Immunity in Ischemia-Free Versus Conventional Liver Transplantation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Resolvin D1 alleviates liver inflammation and fibrosis through SIRT1-mediated NF-κB and TGF-β1/Smads pathways.Journal of inflammation (London, England) · 2026Article
- Role of Histamine in Liver Ischemia-Reperfusion Injury-Implication for H1 Receptor Antagonist in the Clinical Application.Transplantation · 2026Article
- Comprehensive analysis of human hepatotoxicity and mechanism of the plasticizer dimethyl phthalate.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Irisin inhibits adipogenic differentiation of bone marrow mesenchymal stem cells through the SIRT1/RANBP2/FTO signaling axis and protects against osteoporosis.Cell death discovery · 2026Article
- Inhalation of mesenchymal stromal cell-derived extracellular vesicles activates macrophage polarization through the miR-22-3p/NLRP3/IL-1β pathway, ameliorating lung ischemia - reperfusion injury.Stem cell research & therapy · 2026Article
- Functional roles and regulatory mechanisms of paeonol in the treatment of liver disease.Natural products and bioprospecting · 2026Review
- Endothelial-targeted modification of ginseng-derived exosomes for IL-6 SiRNA delivery ameliorates hepatic ischemia-reperfusion injury.Journal of nanobiotechnology · 2026Article
- Integrated network pharmacology and molecular docking reveal multi-target hepatotoxic mechanisms of Xanthii fructus.Medicine · 2025Article
- Exosomal miR-216a-5p targeting TLR-4 alleviates liver ischemia-reperfusion injury by regulating M2 macrophage polarization and neutrophil inflammation.Annals of medicine · 2025Article
- Luteoloside alleviates bleomycin-induced pulmonary fibrosis in mice via SIRT1-mediated protective effect against alveolar epithelial cell senescence.Scientific reports · 2025Article
- The Role of Hepatic SIRT1: From Metabolic Regulation to Immune Modulation and Multi-target Therapeutic Strategies.Journal of clinical and translational hepatology · 2025Review
- Therapeutic applications of exercise in neurodegenerative diseases: focusing on the mechanism of SIRT1.Molecular and cellular biochemistry · 2025Review
- Febuxostat protects from Doxorubicin induced hepatotoxicity in rats via regulation of NF-κB p65/NLRP3 inflammasome and SIRT-1/AMPK pathways.Naunyn-Schmiedeberg's archives of pharmacology · 2025Article
- Gallic Acid and Taurine Attenuate Thiamethoxam-Induced Hepatotoxicity in Rats by Modulating SIRT-1/PGC-1α, NF-κB/iNOS, and p53/Bax/Caspase-3 Pathways.Pharmaceuticals (Basel, Switzerland) · 2025Article
60 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
Abstract
BACKGROUND &
aimsHepatic ischemia-reperfusion injury (IRI), characterized by exogenous antigen-independent local inflammation and hepatocellular death, represents a risk factor for acute and chronic rejection in liver transplantation. We aimed to investigate the molecular communication involved in the mechanism of liver IRI.
methodsWe analyzed human liver transplants, primary murine macrophage cell cultures and IR-stressed livers in myeloid-specific heme oxygenase-1 (HO-1) gene mutant mice, for anti-inflammatory and cytoprotective functions of macrophage-specific HO-1/SIRT1 (sirtuin 1)/p53 (tumor suppressor protein) signaling.
resultsDecreased HO-1 expression in human post-reperfusion liver transplant biopsies correlated with a deterioration in hepatocellular function (serum ALT; p<0.05) and inferior patient survival (p<0.05). In the low HO-1 liver transplant biopsy group, SIRT1/Arf (alternative reading frame)/p53/MDM2 (murine double minute 2) expression levels decreased (p<0.05) while cleaved caspase 3 and frequency of TUNEL+cells simultaneously increased (p<0.05). Immunofluorescence showed macrophages were the principal source of HO-1 in human and mouse IR-stressed livers. In vitro macrophage cultures revealed that HO-1 induction positively regulated SIRT1 signaling, whereas SIRT1-induced Arf inhibited ubiquitinating activity of MDM2 against p53, which in turn attenuated macrophage activation. In a murine model of hepatic warm IRI, myeloid-specific HO-1 deletion lacked SIRT1/p53, exacerbated liver inflammation and IR-hepatocellular death, whereas adjunctive SIRT1 activation restored p53 signaling and rescued livers from IR-damage.
conclusionThis bench-to-bedside study identifies a new class of macrophages activated via the HO-1-SIRT1-p53 signaling axis in the mechanism of hepatic sterile inflammation. This mechanism could be a target for novel therapeutic strategies in liver transplant recipients. LAY SUMMARY: Post-transplant low macrophage HO-1 expression in human liver transplants correlates with reduced hepatocellular function and survival. HO-1 regulates macrophage activation via the SIRT1-p53 signaling network and regulates hepatocellular death in liver ischemia-reperfusion injury. Thus targeting this pathway in liver transplant recipients could be of therapeutic benefit.
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