{
  "abstract": "Ductular reaction-the expansion of reactive bile ductules at the portal-parenchymal interface-has traditionally been interpreted as a proliferative or regenerative response of the biliary epithelium to chronic injury. Here we argue that this histological phenomenon is better understood as a spatial fibrogenic niche: a physically organized, self-reinforcing microenvironment in which reactive cholangiocytes, macrophages, and matrix-producing mesenchymal cells engage in bidirectional signaling that converts repair into fibrosis. We integrate single-cell and spatial transcriptomic evidence showing that reactive cholangiocytes act as a signaling hub, secreting TGF-β, PDGF, CCL2, CXCL chemokines, IL-6, osteopontin, and Hedgehog ligands; that recruited and tissue-resident macrophages amplify this axis; and that portal fibroblasts and hepatic stellate cells close a feed-forward loop by depositing extracellular matrix and growth factors that sustain the niche. We propose that a cholangiocyte-macrophage-fibroblast feed-forward loop, stabilized by chemokine-driven recruitment, TGF-β-centered fibrogenesis, mechanical feedback, and senescence, underlies ductular-associated fibrosis across cholestatic and metabolic liver diseases. Targeting the pathological organization of this niche-rather than any single cell type-may offer a new therapeutic framework for chronic liver fibrosis.",
  "abstract_shown": true,
  "affiliations": [
    "Department of General Hepatobiliary Surgery, Ganmei Hospital Affiliated to Kunming Medical University, Kunming, China.",
    "Institute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China."
  ],
  "article_type": "review article",
  "arxiv": null,
  "author_total": 4,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Kun Wang"
    },
    {
      "affs": [
        1
      ],
      "name": "Linjun Li"
    },
    {
      "affs": [
        0
      ],
      "name": "Xiangkun Mei"
    },
    {
      "affs": [
        0
      ],
      "name": "Hongqiang Gao"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/785pngwy1zqt2.bib",
  "cited_by": 0,
  "doi": "10.3389/fmed.2026.1987203",
  "fulltext_url": "https://europepmc.org/articles/PMC13687942",
  "id": "785pngwy1zqt2",
  "issns": [
    "2296-858X"
  ],
  "landing_url": "https://europepmc.org/article/MED/42923744",
  "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": [
    [
      "openalex",
      "2721|Liver physiology and pathology"
    ]
  ],
  "openalex": "W7221005279",
  "pdf_url": "https://europepmc.org/articles/PMC13687942?pdf=render",
  "pmcid": "PMC13687942",
  "pmid": "42923744",
  "published": "2026-10-08",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/785pngwy1zqt2.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:20:33Z",
      "native_id": "MED:42923744",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42923744"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2721|Liver physiology and pathology",
      "subfield": "general"
    }
  ],
  "title": "Ductular reaction as a spatial fibrogenic niche: cholangiocyte-macrophage-fibroblast crosstalk in chronic liver disease.",
  "title_text": "Ductular reaction as a spatial fibrogenic niche: cholangiocyte-macrophage-fibroblast crosstalk in chronic liver disease.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:20:33Z",
  "url": "https://research.draconitic.com/paper/785pngwy1zqt2",
  "venue": "Frontiers in medicine",
  "versions": []
}