ArticleHepatology (Baltimore, Md.)2016
The neuroimmune guidance cue netrin-1 controls resolution programs and promotes liver regeneration.
Article in Hepatology (Baltimore, Md.), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 63 citations in OpenAlex.
- Inhibition of neogenin fosters resolution of inflammation and tissue regeneration.The Journal of clinical investigation · 2018Trial
- Autocrine Netrin-1 Signaling in Hepatic Stellate Cells Drives Liver Fibrosis and Diet-Induced Metabolic Dysfunction-Associated Steatohepatitis in Mice.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Targeting efferocytosis for tissue regeneration: From microenvironment reprogramming to clinical translation.Theranostics · 2026Review
- Plexin C1 modulates metabolic programming for resolution of severe inflammation.Cell communication and signaling : CCS · 2025Article
- Single-Cell Atlas of Spleen Remodeling Reveals Macrophage Subset-Driven ASFV Pathogenesis.Biology · 2025Article
- Targeting Unc5b in macrophages drives atherosclerosis regression and pro-resolving immune cell function.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Netrin-1 co-cross-linked hydrogel accelerates diabetic wound healing in situ by modulating macrophage heterogeneity and promoting angiogenesis.Bioactive materials · 2024Article
- Efferocytosis in liver disease.JHEP reports : innovation in hepatology · 2024Review
- Insights from the neural guidance factor Netrin-1 into neurodegeneration and other diseases.Frontiers in molecular neuroscience · 2024Review
- Peptidomic Analysis Reveals that Novel Peptide LDP2 Protects Against Hepatic Ischemia/Reperfusion Injury.Journal of clinical and translational hepatology · 2023Article
- Myeloid Trem2 Dynamically Regulates the Induction and Resolution of Hepatic Ischemia-Reperfusion Injury Inflammation.International journal of molecular sciences · 2023Article
- Article
- Responses of hepatic sinusoidal cells to liver ischemia-reperfusion injury.Frontiers in cell and developmental biology · 2023Review
- Activation of the adenosine A2B receptor even beyond the therapeutic window of N-acetylcysteine accelerates liver recovery after an acetaminophen overdose.Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association · 2022Article
- Alternative adenosine Receptor activation: The netrin-Adora2b link.Frontiers in pharmacology · 2022Review
- Myeloid hypoxia-inducible factor HIF1A provides cardio-protection during ischemia and reperfusionFrontiers in cardiovascular medicine · 2022Article
- Netrin-1: A Modulator of Macrophage Driven Acute and Chronic Inflammation.International journal of molecular sciences · 2021Review
- Silencing Myeloid Netrin-1 Induces Inflammation Resolution and Plaque Regression.Circulation research · 2021Article
- PMN-derived netrin-1 attenuates cardiac ischemia-reperfusion injury via myeloid ADORA2B signaling.The Journal of experimental medicine · 2021Article
- Hypoxia-inducible factor-dependent induction of myeloid-derived netrin-1 attenuates natural killer cell infiltration during endotoxin-induced lung injury.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Article
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
unlabelledHepatic ischemia/reperfusion (I/R) is a major adverse reaction to liver transplantation, hemorrhagic shock, or resection. Recently, the anti-inflammatory properties of the axonal guidance cue netrin-1 were reported. Here, we demonstrate that netrin-1 also impacts the resolution of inflammation and promotes hepatic repair and regeneration during liver I/R injury. In initial studies, we investigated the induction of netrin-1 and its receptors in murine liver tissues after I/R injury. Hepatic I/R injury was performed in mice with a partial genetic netrin-1 deficiency (Ntn1(+/-) ) or wild-type C57BL/6 treated with exogenous netrin-1 to examine the endogenous and therapeutically administered impact of netrin-1. These investigations were corroborated by studies determining the characteristics of intravascular leukocyte flow, clearance of apoptotic neutrophils (polymorphonuclear cells [PMNs]), production of specialized proresolving lipid mediators (SPMs), generation of specific growth factors contributing to the resolution of inflammation, and liver repair. Hepatic I/R was associated with a significant reduction of netrin-1 transcript and protein in murine liver tissue. Subsequent studies in netrin-1-deficient mice revealed lower efficacies in reducing PMN infiltration, proinflammatory cytokine levels, and hepatic-specific injury enzymes. Conversely, mice treated with exogenous netrin-1 exhibited increased liver protection and repair, reducing neutrophil influx into the injury site, decreasing proinflammatory mediators, increasing efferocytosis of apoptotic PMNs, and stimulating local endogenous biosynthesis of SPMs and the generation of specific growth factors. Finally, genetic studies implicated the A2B adenosine receptor in netrin-1-mediated protection during hepatic I/R injury.
conclusionThe present study indicates a previously unrecognized role for netrin-1 in liver protection and its contribution to tissue homeostasis and regeneration.
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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.