{
  "abstract": "Peritoneal fibrosis, a major complication of long-term peritoneal dialysis, is driven by transforming growth factor-β1 (TGF-β1)-mediated mesothelial cell dysfunction. Emerging evidence links ferroptosis—a lipid peroxidation-dependent cell death—to fibrotic diseases, but the molecular mechanisms in peritoneal pathology remain unclear. Here, we investigate the role of the STAT1–IRF1–ACSL4 axis in TGF-β1-induced fibrosis and ferroptosis in human peritoneal mesothelial cells (HPMCs). HPMCs were stimulated with TGF-β1 to establish an in vitro fibrosis model and subjected to ACSL4 knockdown, ACSL4 overexpression, or ferroptosis inhibition with Ferrostatin-1. TGF-β1 significantly upregulated fibrosis markers (α-SMA, Collagen I), ferroptosis-related proteins (MDA, 4-HNE, PTGS2), and the STAT1–IRF1 signaling pathway, while suppressing the antioxidant system (GPX4, SLC7A11) (P < 0.001). ACSL4 knockdown markedly restored cell viability, reduced lipid peroxidation, Fe2+ accumulation, ferroptosis activation, and inflammatory cytokine secretion (IL-1β, IL-18) (P < 0.001). In contrast, ACSL4 overexpression exacerbated TGF-β1-induced ferroptosis, fibrosis, and inflammation. Mechanistically, ACSL4 regulated activation of the STAT1–IRF1 axis, as evidenced by changes in STAT1 phosphorylation and IRF1 nuclear translocation. Notably, Ferrostatin-1 reversed ACSL4-induced lipid peroxidation, inhibited STAT1–IRF1 activation, restored GPX4 expression, and attenuated fibrotic and inflammatory responses (P < 0.01). Collectively, these findings demonstrate that the STAT1–IRF1–ACSL4 axis integrates lipid peroxidation-dependent ferroptosis with pro-fibrotic and pro-inflammatory signaling in peritoneal mesothelial cells, identifying ACSL4-centered ferroptotic signaling as a potential therapeutic target for peritoneal fibrosis.\n\nClinical trial number: Not applicable.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Nephrology, Taihe Hospital, Affiliated Hospital of Hubei University of Medicine, Shiyan, China"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 2,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Peng Cheng"
    },
    {
      "affs": [
        0
      ],
      "name": "Qinghong Zhang"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/3kvfqd2ccr6kp.bib",
  "cited_by": 0,
  "doi": "10.1080/0886022x.2026.2748098",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13726331/",
  "id": "3kvfqd2ccr6kp",
  "issns": [
    "0886-022X",
    "1525-6049"
  ],
  "landing_url": "https://doi.org/10.1080/0886022x.2026.2748098",
  "language": "en",
  "licence": "CC-BY-NC-4.0",
  "licence_label": "CC BY-NC 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Basic Sciences Investigations"
    ],
    [
      "heading",
      "Research Article"
    ],
    [
      "openalex",
      "2740|Ferroptosis and cancer prognosis"
    ]
  ],
  "openalex": "W7224873314",
  "pdf_url": "https://www.tandfonline.com/doi/pdf/10.1080/0886022X.2026.2748098?needAccess=true",
  "pmcid": "PMC13726331",
  "pmid": "42960461",
  "published": "2026-10-30",
  "publisher": "Taylor & Francis",
  "ris": "https://research.draconitic.com/paper/3kvfqd2ccr6kp.ris",
  "sources": [
    {
      "first_seen": "2026-11-05T12:22:42Z",
      "native_id": "PMC13726331",
      "source": "pmc",
      "url": "https://doi.org/10.1080/0886022x.2026.2748098"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2740|Ferroptosis and cancer prognosis",
      "subfield": "general"
    }
  ],
  "title": "The STAT1–IRF1–ACSL4 axis drives peritoneal fibrosis and ferroptosis via lipid peroxidation-dependent mechanisms",
  "title_text": "The STAT1–IRF1–ACSL4 axis drives peritoneal fibrosis and ferroptosis via lipid peroxidation-dependent mechanisms",
  "type": "peer-reviewed",
  "updated_at": "2026-11-06T12:22:19Z",
  "url": "https://research.draconitic.com/paper/3kvfqd2ccr6kp",
  "venue": "Renal Failure",
  "versions": []
}