ArticleNature medicine2018
An ALOX12-12-HETE-GPR31 signaling axis is a key mediator of hepatic ischemia-reperfusion injury.
Article in Nature medicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 116 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
116 citing papers in PubMed, 1 synthesis or guideline pooled it, 224 citations in OpenAlex.
- Incidence, risk factors, and prognosis of abnormal liver biochemical tests in COVID-19 patients: a systematic review and meta-analysis.Hepatology international · 2020Pooled it
- Ya-Jie-Sha-Ba Decoction Regulates Arachidonic Acid Metabolism to Treat Alcohol-Associated Liver Disease by Activating PPARα-CYP4A14 Axis: Insights From Multi-Omics Analysis and Experimental Validations.Journal of cellular and molecular medicine · 2026Article
- Article
- Effects of Normothermic Hepatic Ischemia-Reperfusion Injury on the Hepatic Disposition of Arachidonic Acid and Its Cytochrome P450-Generated Metabolites in Rats.Pharmaceutical research · 2026Article
- Metabolomic signatures for diagnosis and clinical severity in Parkinson's disease.EBioMedicine · 2026Article
- Article
- International Union of Basic and Clinical Pharmacology. CXXII. Applying an objective evaluation to the status of class A orphan G protein-coupled receptors.Pharmacological reviews · 2026Review
- Tumour-associated high endothelial venules drive portal-specific immune evasion in lymph nodes via ALOX12.Nature communications · 2026Article
- Advancements in Understanding the Role of Oxylipins in Liver Injury and Liver Failure.Journal of clinical and translational hepatology · 2026Review
- The Simultaneous Prevention of Multiple Diseases: A "One Ring to Rule Them All" Framework for Redox-Driven Health and Longevity.Nutrients · 2026Review
- Gut Microbiota-Non-Coding RNA Axis in Immune Modulation and Disease: From Mechanisms to Clinical Translation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Imaging bioactive lipid isomers in acetaminophen-induced liver injury using nano-DESI tandem MS.Journal of lipid research · 2026Article
- Enterococcus faecalis-induced bystander effect causes epigenetic alterations leading to aberrant TGF-β signaling and epithelial-mesenchymal transition.Cell communication and signaling : CCS · 2026Article
- Article
- Multi-omics analysis unveils inflammatory and metabolic alterations between the synovium and cartilage in patients with knee osteoarthritis.Frontiers in molecular biosciences · 2026Article
- Damage-associated molecular patterns in hepatic ischemia-reperfusion injury: spatiotemporal signatures, biomarker potential, and clinical translation.Frontiers in immunology · 2026Review
- Serum Metabolomic Profiling Reveals Potential Mechanisms and Biomarkers of Seladelpar Treatment in Patients With Primary Biliary Cholangitis.PPAR research · 2026Article
- Ursolic acid mitigates hepatic ischemia-reperfusion injury by regulating the ALOX12/12(S)-HETE and PTGES/prostaglandin E2 axis via arachidonic acid metabolism pathway.Frontiers in pharmacology · 2026Article
- The role of ALOX15 in inflammation-related diseases.Frontiers in immunology · 2026Review
- Emerging Roles and Possible Therapeutic Applications of Arachidonic Acid Metabolites in Sepsis and Sepsis-Associated Organ Dysfunction.Drug design, development and therapy · 2026Review
56 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
- Commented on by
Authors and funding
22 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hepatic ischemia-reperfusion (IR) injury is a common clinical issue lacking effective therapy and validated pharmacological targets. Here, using integrative 'omics' analysis, we identified an arachidonate 12-lipoxygenase (ALOX12)-12-hydroxyeicosatetraenoic acid (12-HETE)-G-protein-coupled receptor 31 (GPR31) signaling axis as a key determinant of the hepatic IR process. We found that ALOX12 was markedly upregulated in hepatocytes during ischemia to promote 12-HETE accumulation and that 12-HETE then directly binds to GPR31, triggering an inflammatory response that exacerbates liver damage. Notably, blocking 12-HETE production inhibits IR-induced liver dysfunction, inflammation and cell death in mice and pigs. Furthermore, we established a nonhuman primate hepatic IR model that closely recapitulates clinical liver dysfunction following liver resection. Most strikingly, blocking 12-HETE accumulation effectively attenuated all pathologies of hepatic IR in this model. Collectively, this study has revealed previously uncharacterized metabolic reprogramming involving an ALOX12-12-HETE-GPR31 axis that functionally determines hepatic IR procession. We have also provided proof of concept that blocking 12-HETE production is a promising strategy for preventing and treating IR-induced liver damage.
Indexed as
Identifiers
What OpenQuestion holds
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.