ArticleHepatology (Baltimore, Md.)2019
Spermidine Confers Liver Protection by Enhancing NRF2 Signaling Through a MAP1S-Mediated Noncanonical Mechanism.
Article in Hepatology (Baltimore, Md.), 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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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.
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Who cites it
43 citing papers in PubMed, 72 citations in OpenAlex.
- Gut microbiota-derived metabolites as context-dependent modulators of Nrf2 signaling in inflammation-driven carcinogenesis.Gut microbes · 2026Review
- Liver fibrosis: Pathogenesis and innovative nanoparticle-based therapeutic strategies.International journal of pharmaceutics: X · 2026Review
- Spermidine Alleviates Liver Damage Induced by Iron Overload by Inhibiting Oxidative Stress.Biological trace element research · 2026Article
- Babao Dan Improves Doxorubicin-Induced Cardiomyopathy by Activating Nrf2/GPX4 Signaling Pathway.Chinese journal of integrative medicine · 2026Article
- Sheep-derived probiotics alleviate weaning-induced oxidative stress in lambs via the gut-liver axis.NPJ biofilms and microbiomes · 2026Article
- Spermidine suppresses liver fibrosis by remodeling the communication signal between liver sinusoidal endothelial cells and hepatic stellate cells.Cell death discovery · 2026Article
- Taxifolin and Astilbin Protect Against Cadmium-Induced Oxidative Stress and Apoptosis in Chicken Liver Cells via Nrf2/HO-1 Signaling.Biological trace element research · 2026Article
- Gut microbial metabolites of amino acids in liver diseases.Gut microbes · 2025Review
- Spermidine-encapsulated chondroitin sulfate methacryloyl hydrogel delivery system for remodeling bone homeostasis in rheumatoid arthritis.Materials today. Bio · 2025Article
- Cell-specific roles of autophagy in liver fibrosis: implications for targeted pharmacotherapy.Annals of medicine · 2025Review
- Ferroptosis in liver fibrosis and its potential intervention strategy.Cell biology and toxicology · 2025Review
- Reactive Oxygen Species-Mediated TRPM2 Activation Facilitates Phagocytosis of Macrophages to Reverse Profibrotic Phenotype.Liver international : official journal of the International Association for the Study of the Liver · 2025Article
- Pharmacometabolomics uncovers key metabolic changes in the first-in-human study of β-lapachone derivative.Metabolomics : Official journal of the Metabolomic Society · 2025Article
- Food Nutrients and Bioactive Compounds for Managing Metabolic Dysfunction-Associated Steatotic Liver Disease: A Comprehensive Review.Nutrients · 2025Review
- Calorie restriction mimetics against aging and inflammation.Biogerontology · 2025Review
- Spermidine inactivates proteasome activity and enhances ferroptosis in prostate cancer.Acta pharmaceutica Sinica. B · 2025Article
- CT-sensitized nanoprobe for effective early diagnosis and treatment of pulmonary fibrosis.Journal of nanobiotechnology · 2025Article
- Protocatechuic acid relieves ferroptosis in hepatic lipotoxicity and steatosis via regulating NRF2 signaling pathway.Cell biology and toxicology · 2024Article
- Rational engineering of homospermidine synthase for enhanced catalytic efficiency toward spermidine synthesis.Synthetic and systems biotechnology · 2024Article
- Arginase 2 attenuates ulcerative colitis by antioxidant effects of spermidine.Journal of gastroenterology · 2024Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Spermidine (SPD), a naturally occurring polyamine, has been recognized as a caloric restriction mimetic that confers health benefits, presumably by inducing autophagy. Recent studies have reported that oral administration of SPD protects against liver fibrosis and hepatocarcinogenesis through activation of microtubule associated protein 1S (MAP1S)-mediated autophagy. Nuclear factor (erythroid-derived 2)-like 2 (NRF2) is a transcription factor that mediates cellular protection by maintaining the cell's redox, metabolic, and proteostatic balance. In this study, we demonstrate that SPD is a noncanonical NRF2 inducer, and that MAP1S is a component of this noncanonical pathway of NRF2 activation. Mechanistically, MAP1S induces NRF2 signaling through two parallel mechanisms, both resulting in NRF2 stabilization: (1) MAP1S competes with Kelch-like ECH-associated protein 1 (KEAP1) for NRF2 binding through an ETGE motif, and (2) MAP1S accelerates p62-dependent degradation of KEAP1 by the autophagy pathway. We further demonstrate that SPD confers liver protection by enhancing NRF2 signaling. The importance of both NRF2 and p62-dependent autophagy in SPD-mediated liver protection was confirmed using a carbon tetrachloride-induced liver fibrosis model in wild-type, Nrf2
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