{
  "abstract": "Extracellular high mobility group box 1 (HMGB1) serves as a key damage-associated molecular pattern that drives the pathological process of inflammatory liver injury; however, its role in liver fibrosis and the underlying mechanisms need to be elucidated. To investigate the proinflammatory and profibrotic roles of extracellular HMGB1, we used an adenovirus-mediated system to measure HMGB1 secretion in mice. We subsequently constructed two recombinant proteins, PfTrx-HMGB1¹⁷(95 - 111) and HBcΔ-HMGB1³⁴(150 - 183), targeting the interactions of HMGB1 with its receptors, namely, toll-like receptor 4 (TLR4) and receptor for advanced glycation end products (RAGE), respectively. Mice were immunized with the two recombinant proteins to assess neutralizing antibody induction and the protective effects of the HMGB1 vaccines against carbon tetrachloride (CCl₄)-induced liver fibrosis. Our results revealed the nucleocytoplasmic translocation of HMGB1 in the livers of both humans and mice with fibrosis. Extracellular HMGB1 induced liver inflammation and fibrogenesis in mice. Immunization with the two HMGB1 vaccines resulted in the production of high levels of anti-HMGB1 neutralizing antibodies, which inhibited the activation of hepatic stellate cells (LX-2) and the production of proinflammatory and profibrotic factors in RAW 264.7 cells. Furthermore, vaccination with these compounds significantly protected against CCl₄-induced liver injury, inflammation, and fibrosis in mice. These findings demonstrate that extracellular HMGB1, by binding to TLR4 or RAGE, is pivotal in driving liver inflammation and fibrosis. Vaccination against HMGB1 through disruption of interaction with TLR4 or RAGE represents a promising therapeutic strategy for hepatic fibrosis.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Rheumatology, The First Affiliated Hospital of Xi'an Jiaotong University, 277 West Yanta Road, Xi'an, Shaanxi, 710061, China.",
    "Center of Reproductive Medicine, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, China.",
    "Department of Rehabilitation Medicine, Shaanxi Provincial People's Hospital, Xi'an, China.",
    "Department of Rheumatology, The First Affiliated Hospital of Xi'an Jiaotong University, 277 West Yanta Road, Xi'an, Shaanxi, 710061, China. haozhm66@126.com."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 9,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Qian Li"
    },
    {
      "affs": [
        0
      ],
      "name": "Hanchao Li"
    },
    {
      "affs": [
        1
      ],
      "name": "Yongwei Huo"
    },
    {
      "affs": [
        1
      ],
      "name": "Hong Tian"
    },
    {
      "affs": [
        0
      ],
      "name": "Li Zhu"
    },
    {
      "affs": [
        0
      ],
      "name": "Xiaoyan Zheng"
    },
    {
      "affs": [
        0
      ],
      "name": "Wengang Sun"
    },
    {
      "affs": [
        2
      ],
      "name": "Xueting Zhang"
    },
    {
      "affs": [
        3
      ],
      "name": "Zhiming Hao",
      "orcid": "0000-0003-4046-5921"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/dvd5w0x1gkfe2.bib",
  "cited_by": 0,
  "doi": "10.1007/s10753-026-02578-4",
  "fulltext_url": "https://europepmc.org/articles/PMC13719786",
  "id": "dvd5w0x1gkfe2",
  "issns": [
    "0360-3997",
    "1573-2576"
  ],
  "landing_url": "https://europepmc.org/article/MED/42955153",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Research"
    ],
    [
      "openalex",
      "2721|Liver physiology and pathology"
    ]
  ],
  "openalex": "W7172098378",
  "pdf_url": "https://europepmc.org/articles/PMC13719786?pdf=render",
  "pmcid": "PMC13719786",
  "pmid": "42955153",
  "published": "2026-08-01",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/dvd5w0x1gkfe2.ris",
  "sources": [
    {
      "first_seen": "2026-11-01T00:20:47Z",
      "native_id": "MED:42955153",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42955153"
    },
    {
      "first_seen": "2026-11-02T12:23:41Z",
      "native_id": "PMC13719786",
      "source": "pmc",
      "url": "https://doi.org/10.1007/s10753-026-02578-4"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2721|Liver physiology and pathology",
      "subfield": "general"
    }
  ],
  "title": "Vaccination Against HMGB1 Protects Mice from CCl₄-Induced Liver Injury, Inflammation, and Fibrosis.",
  "title_text": "Vaccination Against HMGB1 Protects Mice from CCl₄-Induced Liver Injury, Inflammation, and Fibrosis.",
  "type": "peer-reviewed",
  "updated_at": "2026-11-03T12:20:47Z",
  "url": "https://research.draconitic.com/paper/dvd5w0x1gkfe2",
  "venue": "Inflammation",
  "versions": []
}