ArticleExperimental & molecular medicine2023
HMGB1 induces hepcidin upregulation in astrocytes and causes an acute iron surge and subsequent ferroptosis in the postischemic brain.
Article in Experimental & molecular medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 51 citations in OpenAlex.
- Rescuing anxiety by targeting the neuronal-astrocytic iron signaling axis in male mice.Signal transduction and targeted therapy · 2026Article
- NEMO (IKKγ) citrullination in microglia promotes neuroinflammation in the post-ischemic brain.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Article
- Danshen (Antioxidants (Basel, Switzerland) · 2026Article
- Anti-HMGB1 Antibody Therapy Ameliorates Depression Following Spinal Cord Injury in Rats by Inhibiting Ferroptosis.Journal of cellular and molecular medicine · 2026Article
- Interference with HMGB1 Inhibits Neuronal Ferroptosis Following Spinal Cord Injury through Targeting ACSL4.Neurochemical research · 2026Article
- Ginsenosides exhibit potential therapeutic potential in photoaging by regulating keratinocyte ferroptosis.Journal of ginseng research · 2026Article
- HMGB1-mediated enhancement of glycolysis activates hepatic stellate cells by inhibiting ferroptosis in alcoholic hepatic fibrosis.Stem cell research & therapy · 2026Article
- The Mechanism of Ferroptosis and Blood-Brain Barrier Damage in Cerebrovascular Diseases.Biomedicines · 2026Review
- Damage-Associated Molecular Patterns in Perioperative Anesthesia Care: A Clinical Perspective.Anesthesia research · 2026Article
- The redox-sensitive protein HMGB1: intracellular and extracellular roles.Experimental & molecular medicine · 2026Review
- Meningeal Lymphatics Drives Macrophage Clearance via CCL2-CCR2 Axis After Cerebral Ischemia.Current issues in molecular biology · 2026Article
- Dual role of lactate in ferroptosis: Mechanisms, pathophysiology and therapeutic opportunities (Review).International journal of molecular medicine · 2026Review
- The vicious cycle of neuroinflammation and ferroptosis in depression: mechanisms and therapeutic targets.Frontiers in neuroscience · 2026Review
- Potential crosstalk between ferroptosis and immunosenescence in osteoarthritis: evidence integration and translational insights from the osteoimmune microenvironment.Frontiers in immunology · 2026Review
- From scavenger to victim: mechanism and treatment of microglial ferroptosis in white matter injury disease.Frontiers in immunology · 2026Review
- Metabolic Regulatory Networks in Ferroptosis During Alzheimer's Disease, Mechanisms of Glial Cell Action, and Pathological Correlations with Neuritic Plaques.International journal of general medicine · 2026Review
- Multidimensional iron dysmetabolism and gut-brain axis interactions in restless legs syndrome: from peripheral deficiency to central dysregulation.Frontiers in aging neuroscience · 2026Review
- Hyperbaric oxygen therapy in alleviating cerebral ischemia-reperfusion injury via the BMP6/Smad-hepcidin pathway.PloS one · 2026Article
- Muscle Structure and Function Recovery: Adalimumab-Calcium Channel Synergy in Post-Ischemic Stroke Sarcopenia.Journal of cachexia, sarcopenia and muscle · 2025Article
- Ferroptosis in Human Diseases: Fundamental Roles and Emerging Therapeutic Perspectives.Antioxidants (Basel, Switzerland) · 2025Review
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Dysregulation of brain iron levels causes functional disturbances and damages neurons. Hepcidin (a peptide hormone) plays a principal role in regulating intracellular iron levels by modulating ferroportin (FPN, the only known iron exporter) through triggering its internalization and lysosomal degradation. We observed a significant and rapid iron surge in the cortices of ischemic hemispheres at 3 h after cerebral ischemia (middle cerebral artery occlusion, MCAO) that was maintained until 4 d post-MCAO. We showed upregulation of hepcidin expression in the brain as early as 3 h post-MCAO, mainly in astrocytes, and significant hepcidin accumulation in serum from 6 h post-MCAO, and these inductions were maintained for 1 day and 7 days, respectively. High mobility group box 1 (HMGB1), a prototypic danger-associated molecular pattern, accumulates markedly after transient MCAO and plays critical roles in damage aggravation via its proinflammatory effects. Here, we demonstrated that treatment with recombinant HMGB1 stimulated astrocytes to induce hepcidin expression in a TLR4- and CXCR4-dependent manner. Furthermore, hepcidin-mediated intracellular iron accumulation in neurons was confirmed by an experiment using N-methyl-D-aspartate (NMDA)-conditioned medium-treated primary astrocytes and fresh primary cortical neurons treated with hepcidin-containing astrocyte-conditioned medium. Moreover, HMGB1-mediated local hepcidin upregulation and subsequent local iron surge were found to cause ferroptosis in the postischemic brain, which was suppressed by the functional blocking of HMGB1 using intranasally administered HMGB1 A box or anti-HMGB1 antibody. These findings show that HMGB1 serves as a ferroptosis inducer by upregulating hepcidin in astrocytes and thus aggravates acute damage in the postischemic brain.
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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.