High mobility group box 1 (HMGB1)
HMGB1 (high-mobility group box 1) is a highly conserved nuclear protein that functions primarily as a chromatin-associated DNA-binding factor, but it is also widely recognized as an extracellular signaling molecule.
HMGB1 (high-mobility group box 1) is a highly conserved nuclear protein that functions primarily as a chromatin-associated DNA-binding factor, but it is also widely recognized as an extracellular signaling molecule. In the nucleus, HMGB1 helps organize chromatin and modulate transcriptional accessibility. When released from stressed, damaged, or dying cells, it can act as an alarmin or damage-associated molecular pattern, promoting inflammatory signaling through receptors such as receptor for advanced glycation end products (RAGE) and, in broader inflammatory contexts, pathways involving toll like receptor 4 (TLR4).
In biomedical research, HMGB1 is frequently studied as a mediator of inflammation, tissue injury, and immunogenic cell death. Its extracellular release is often associated with immune activation, while intracellular regulation of HMGB1, including acetylation status and subcellular localization, can influence inflammatory outcomes. Because of these roles, HMGB1 has become a target of interest in cancer immunotherapy, sepsis, liver injury, disc degeneration, and neonatal inflammatory conditions.
Where the papers sit
10 papers from the last 6 months study High mobility group box 1 (HMGB1) directly · updated from PubMed 12 Oct 2026
Study type 0 clinical trials · 1 observational · 3 human data · 5 preclinical · 1 unclassified
Themes 3 themes · 1 new direction
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HMGB1-Centered Inflammatory Signaling
HMGB1-centered inflammatory signaling is being connected to ferroptosis, microglial activation, and metabolic dysfunction across brain and reproductive tissues. In metabolic syndrome-associated cognitive impairment, HMGB1 aggravates neuronal ferroptosis and microglial inflammation through TLR4, with NRF2-autophagy appearing as a protective axis. Related work links HMGB1 signaling to insulin resistance in ovarian granulosa cells in PCOS and to exosome-associated depressive behavior after arthritis. Pharmacologic receptor modulation and lncRNA-targeted approaches are gaining attention, but the shared mechanisms and translational relevance across these disorders remain unresolved.
4 papers · 40%
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Cancer Immune Resistance and Radiotherapy
HMGB1 is emerging as a link between tumor metabolism, DNA repair, treatment resistance, and antitumor immunity. In colorectal and rectal cancer, EFHD2-driven lactate signaling uses HMGB1 and HIF-1α to support DNA damage repair and radioresistance, while serial HMGB1 measurement is being related to MRI response and ctDNA. In hepatocellular carcinoma, cysteine-metabolism reprogramming is associated with anti-PD-1 resistance and progression. The field is moving toward HMGB1-informed combinations and biomarkers, but the predictive value of circulating HMGB1 remains open.
3 papers · 30%
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HMGB1 in Inflammatory Injury
Serum HMGB1 is being evaluated as a marker of inflammatory and tissue-injury severity, especially in COPD with pulmonary hypertension and neonatal jaundice. Associations with PCO2, TNF-α, VEGF, interleukins, and phototherapy response support clinical correlation but not a unified diagnostic use. In heat stroke, ALKBH5-mediated m6A demethylation stabilizes HMGB1 and drives hepatocyte pyroptosis and liver injury. The shared question is whether HMGB1 can move from an associated serum signal to a mechanistically actionable target.
3 papers · 30%
Joint-derived exosomes make HMGB1 a vesicular mediator of arthritis-associated depressive behavior
The mono-iodoacetate arthritis mouse model shows that HMGB1 need not act only as a soluble inflammatory signal or biomarker: it is displayed on the exterior of joint-derived exosomes, transported to the brain, and delivered to neurons, where it activates NF-κB and senescence programs that produce depressive-like behavior. Blocking exosome release or neutralizing HMGB1 prevented these neuronal and behavioral effects, whereas transferring the exosomes to naïve mice reproduced them, establishing an inter-organ, vesicle-mediated role for HMGB1 beyond the local inflammatory and disease processes represented elsewhere in the set 42107473May.
Papers
The 10 papers from the last 6 months that study High mobility group box 1 (HMGB1) directly, newest first, by theme and by study type. Study types come from PubMed publication types and MeSH headings.
By theme
HMGB1-Centered Inflammatory Signaling (4)
- HMGB1 aggravates neuronal ferroptosis and microglial inflammation in metabolic syndrome-associated cognitive impairment via the NRF2-autophagic flux axis. Molecular biomedicine · 18 Aug 2026 PMID 42608631
- Targeting Long Noncoding RNA LUCAT1 Alleviates Insulin Resistance of Ovarian Granulosa Cells in Polycystic Ovary Syndrome by Blocking HMGB1-Mediated Autophagy. American journal of reproductive immunology (New York, N.Y. : 1989) · 1 Jul 2026 PMID 42381638
- Exosomes from joints mediate depressive-like behaviors in MIA arthritis mice. Brain research bulletin · 10 May 2026 PMID 42107473
- Dually Charged Dendrimeric Polyglycerol Modulates Interleukin-33 at Alarmin Receptors in Microglia. ACS chemical neuroscience · 4 May 2026 PMID 42081615
Cancer Immune Resistance and Radiotherapy (3)
- Weekly measurement of HMGB1 during neoadjuvant chemoradiotherapy in rectal cancer patients: correlations with MRI response and ctDNA. Radiology and oncology · 26 Jun 2026 PMID 42359756
- EFHD2 drives lactate-mediated DNA damage repair and immunosuppression via HMGB1 and HIF-1α to confer radioresistance in colorectal cancer. Cell death & disease · 23 Jun 2026 PMID 42336814
- WNK4 Enhances Anti-PD-1 Resistance and Promotes Tumor Progression in Hepatocellular Carcinoma by Reprogramming Cysteine Metabolism in Cancer-Associated Fibroblasts. FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 8 Jun 2026 PMID 42253146
HMGB1 in Inflammatory Injury (3)
- Utility of serum HMGB1 in chronic obstructive pulmonary disease with pulmonary hypertension: A single-centre analysis. Pulmonology · 21 Aug 2026 PMID 42625546
- Serum HMGB1 and sCD14 levels in neonates with jaundice: associations with disease severity and phototherapy efficacy. The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians · 26 May 2026 PMID 42186388
- ALKBH5-Mediated m6A Demethylation Stabilizes HMGB1 to Drive Hepatocyte Pyroptosis and Liver Injury in Heat Stroke: Targeting via Biomimetic Nanodelivery. Antioxidants & redox signaling · 19 May 2026 PMID 42156334
By study type
Observational studies and case reports (1)
- Serum HMGB1 and sCD14 levels in neonates with jaundice: associations with disease severity and phototherapy efficacy. The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians · 26 May 2026 PMID 42186388
Human data, design not indexed (3)
- Utility of serum HMGB1 in chronic obstructive pulmonary disease with pulmonary hypertension: A single-centre analysis. Pulmonology · 21 Aug 2026 PMID 42625546
- Targeting Long Noncoding RNA LUCAT1 Alleviates Insulin Resistance of Ovarian Granulosa Cells in Polycystic Ovary Syndrome by Blocking HMGB1-Mediated Autophagy. American journal of reproductive immunology (New York, N.Y. : 1989) · 1 Jul 2026 PMID 42381638
- Weekly measurement of HMGB1 during neoadjuvant chemoradiotherapy in rectal cancer patients: correlations with MRI response and ctDNA. Radiology and oncology · 26 Jun 2026 PMID 42359756
Preclinical: animal, cell and lab studies (5)
- HMGB1 aggravates neuronal ferroptosis and microglial inflammation in metabolic syndrome-associated cognitive impairment via the NRF2-autophagic flux axis. Molecular biomedicine · 18 Aug 2026 PMID 42608631
- WNK4 Enhances Anti-PD-1 Resistance and Promotes Tumor Progression in Hepatocellular Carcinoma by Reprogramming Cysteine Metabolism in Cancer-Associated Fibroblasts. FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 8 Jun 2026 PMID 42253146
- ALKBH5-Mediated m6A Demethylation Stabilizes HMGB1 to Drive Hepatocyte Pyroptosis and Liver Injury in Heat Stroke: Targeting via Biomimetic Nanodelivery. Antioxidants & redox signaling · 19 May 2026 PMID 42156334
- Exosomes from joints mediate depressive-like behaviors in MIA arthritis mice. Brain research bulletin · 10 May 2026 PMID 42107473
- Dually Charged Dendrimeric Polyglycerol Modulates Interleukin-33 at Alarmin Receptors in Microglia. ACS chemical neuroscience · 4 May 2026 PMID 42081615
Unclassified: not yet indexed with MeSH (1)
- EFHD2 drives lactate-mediated DNA damage repair and immunosuppression via HMGB1 and HIF-1α to confer radioresistance in colorectal cancer. Cell death & disease · 23 Jun 2026 PMID 42336814
Written from 10 PubMed abstracts, each one listed by PMID above. Published: 2026-06-16. Last written: 2026-08-26 by GPT. Drafted by language models from published abstracts; not medical advice.