{
  "abstract": "Pulmonary fibrosis is a common pathological endpoint of several interstitial lung diseases. Idiopathic pulmonary fibrosis (IPF), in particular, has an unknown cause, produces progressive scarring of the lung parenchyma, and carries a poor prognosis. Single-cell and spatial omics studies have shown that lung fibroblasts comprise multiple populations with distinct anatomical locations and functional states. However, how these states are established, interconverted, and maintained in the injured microenvironment remains incompletely understood and has not been directly validated. This review uses IPF as the primary clinical context and draws complementary mechanistic evidence from other fibrotic lung diseases and animal models. It examines fibroblast origins and state heterogeneity; signaling networks involving transforming growth factor-β (TGF-β), Wnt, and Yes-associated protein (YAP); interactions among epithelial cells, immune cells, and fibroblasts; and epigenetic and metabolic remodeling. On this basis, we propose a two-layer stability model of epigenetic maintenance and signaling feedback as a working framework for understanding the persistence of profibrotic states. We also discuss how treatment might move from nonselective inhibition toward restricting pathological states, eliminating pathogenic subpopulations, and preserving reparative function. The causal sequence proposed by this model, the necessity of its components, and the thresholds for state reversal remain unresolved and require testing through lineage tracing, assessment of phenotypic stability after stimulus withdrawal, and sequential combination interventions.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Guilin Medical University, Guilin 541199, China",
    "The Laboratory of Respiratory Disease, The Affiliated Hospital of Guilin Medical University, Guilin 541001, China",
    "The Key Laboratory of Respiratory Diseases (Guilin Medical University), Education Department of Guangxi Zhuang Autonomous Region, Guilin 541001, China",
    "Guangxi Key Laboratory of Metabolic Reprogramming and Intelligent Medical Engineering for Chronic Diseases, Guilin Medical University, Guilin 541199, China",
    "Guangxi Clinical Research Center for Diabetes and Metabolic Diseases, Guangxi Health Commission Key Laboratory of Glucose and Lipid Metabolism Disorders, The Second Affiliated Hospital of Guilin Medical University, Guilin 541199, China",
    "School of Artificial Intelligence in Medicine, Guilin Medical University, Guilin 541199, China"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 8,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Lincha Tian"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Xinru Feng"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Bo Xiao"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Lixia Hou"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Xiulin Yi"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Manjie Chen"
    },
    {
      "affs": [
        1,
        2,
        3,
        4
      ],
      "name": "Biwen Mo"
    },
    {
      "affs": [
        0,
        2,
        3,
        4,
        5
      ],
      "name": "Dong Yao",
      "orcid": "0000-0001-8883-5384"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/18gv4p2aq6v0n.bib",
  "cited_by": 0,
  "doi": "10.3390/ijms272110031",
  "fulltext_url": null,
  "id": "18gv4p2aq6v0n",
  "issns": [
    "1422-0067"
  ],
  "landing_url": "https://www.mdpi.com/1422-0067/27/21/10031",
  "language": null,
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [],
  "openalex": null,
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-11-09",
  "publisher": "MDPI AG",
  "ris": "https://research.draconitic.com/paper/18gv4p2aq6v0n.ris",
  "sources": [
    {
      "first_seen": "2026-11-09T12:22:39Z",
      "native_id": "10.3390/ijms272110031",
      "source": "crossref",
      "url": "https://www.mdpi.com/1422-0067/27/21/10031"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "issn:1422-0067",
      "subfield": "general"
    }
  ],
  "title": "Pulmonary Fibroblast Heterogeneity and Functional Remodeling in Idiopathic Pulmonary Fibrosis: State Persistence and Reversibility",
  "title_text": "Pulmonary Fibroblast Heterogeneity and Functional Remodeling in Idiopathic Pulmonary Fibrosis: State Persistence and Reversibility",
  "type": "peer-reviewed",
  "updated_at": "2026-11-09T12:22:39Z",
  "url": "https://research.draconitic.com/paper/18gv4p2aq6v0n",
  "venue": "International Journal of Molecular Sciences",
  "versions": []
}