ArticleHepatology (Baltimore, Md.)2020
Human Antigen R (HuR): A Regulator of Heme Oxygenase-1 Cytoprotection in Mouse and Human Liver Transplant 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 18 papers.
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Who cites it
18 citing papers in PubMed, 24 citations in OpenAlex.
- Article
- Changes in iron metabolism after primary PCI in patients with STEMI and ischemia-reperfusion injury.Experimental and therapeutic medicine · 2026Article
- Understanding metabolic resilience by unraveling temporal dynamics of cellular responses.Trends in endocrinology and metabolism: TEM · 2025Review
- Posttranscriptional control of hepatic CEACAM1 3'UTR by human antigen R (HuR) mitigates sterile liver inflammation.JCI insight · 2025Article
- Article
- Multifaceted Nature of HuR in Atherosclerosis Development.Current medicinal chemistry · 2025Review
- Mechanistic Insights into Alternative Gene Splicing in Oxidative Stress and Tissue Injury.Antioxidants & redox signaling · 2024Review
- Transcriptional Profiling Underscores the Role of Preprocurement Allograft Metabolism and Innate Immune Status on Outcomes in Human Liver Transplantation.Annals of surgery open : perspectives of surgical history, education, and clinical approaches · 2024Article
- Interaction between ischemia-reperfusion injury and intestinal microecology in organ transplantation and its therapeutic prospects.Frontiers in immunology · 2024Review
- Role of the immune system in liver transplantation and its implications for therapeutic interventions.MedComm · 2023Review
- Alternative splicing of CEACAM1 by hypoxia-inducible factor-1α enhances tolerance to hepatic ischemia in mice and humans.Science translational medicine · 2023Article
- MCD Diet Modulates HuR and Oxidative Stress-Related HuR Targets in Rats.International journal of molecular sciences · 2023Article
- Liver ischaemia-reperfusion injury: a new understanding of the role of innate immunity.Nature reviews. Gastroenterology & hepatology · 2022Review
- Protective effects of gastrodin pretreatment on mouse hepatic ischemia-reperfusion occurring through antioxidant and anti-apoptotic mechanisms.Experimental and therapeutic medicine · 2021Article
- Lycopene alleviates hepatic ischemia reperfusion injury via the Nrf2/HO-1 pathway mediated NLRP3 inflammasome inhibition in Kupffer cells.Annals of translational medicine · 2021Article
- Hypoxia-inducible factor-1α-dependent induction of miR122 enhances hepatic ischemia tolerance.The Journal of clinical investigation · 2021Article
- mRNA Post-Transcriptional Regulation by AU-Rich Element-Binding Proteins in Liver Inflammation and Cancer.International journal of molecular sciences · 2020Review
- New therapeutic concepts against ischemia-reperfusion injury in organ transplantation.Expert review of clinical immunologyReview
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
Abstract
BACKGROUND AND
aimsIschemia-reperfusion injury (IRI) represents a risk factor in liver transplantation (LT). We have shown that overexpression of heme oxygenase-1 (HO-1) mitigates hepatic IRI in LT recipients. Here, we hypothesized that human antigen R (HuR), the stabilizer of adenylate-uridylate (AU)-rich mRNAs, is required for hepatoprotection in LT. APPROACH AND
resultsIn an experimental arm, HuR/HO-1 protein expression was correlated with hepatic IRI phenotype. In an in vitro inflammation mimic model of hepatic warm IRI, induction of HuR/HO-1 and cytoplasmic localization following cytokine preconditioning were detected in primary hepatocyte cultures, whereas HuR silencing caused negative regulation of HO-1, followed by enhanced cytotoxicity. Using the HuR-inhibitor, we showed that HuR likely regulates HO-1 through its 3' untranslated region and causes neutrophil activation (CD69+/lymphocyte antigen 6 complex locus G [Ly6-G]). HuR silencing in bone marrow-derived macrophages decreased HO-1 expression, leading to the induction of proinflammatory cytokines/chemokines. RNA sequencing of HuR silenced transcripts under in vitro warm IRI revealed regulation of genes thymus cell antigen 1 (THY1), aconitate decarboxylase 1 (ACOD1), and Prostaglandin E Synthase (PTGES). HuR, but not hypoxia-inducible protein alpha, positively regulated HO-1 in warm, but not cold, hypoxia/reoxygenation conditions. HuR modulated HO-1 in primary hepatocytes, neutrophils, and macrophages under reperfusion. Adjunctive inhibition of HuR diminished microtubule-associated proteins 1A/1B light chain 3B (LC3B), a marker for autophagosome, under HO-1 regulation, suggesting a cytoprotective mechanism in hepatic IR. In a clinical arm, hepatic biopsies from 51 patients with LT were analyzed at 2 hours after reperfusion. Graft HuR expression was negatively correlated with macrophage (CD80/CD86) and neutrophil (Cathepsin G) markers. Hepatic IRI increased HuR/HO-1 expression and inflammatory genes. High HuR-expressing liver grafts showed lower serum alanine aminotransferase/serum aspartate aminotransferase levels and improved LT survival.
conclusionsThis translational study identifies HuR as a regulator of HO-1-mediated cytoprotection in sterile liver inflammation and a biomarker of ischemic stress resistance in LT.
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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.