{
  "abstract": "Background\n\nPrimary sclerosing cholangitis (PSC) remains a challenging biliary disease characterized by persistent inflammation and extensive fibrosis. However, its molecular drivers are not fully understood. Here, we explored the functional significance of NAD(P)H:quinone oxidoreductase 1 (NQO1) in the progression of PSC.Methods\n\nWild-type (WT) and Nqo1 knockout (NKO) male mice were fed a diet containing 0.1% (w/w) 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) for 1 or 3 weeks to induce cholestatic liver injury. Liver tissues and plasma samples were collected for biochemical, histological, and molecular analyses. To further investigate the underlying mechanisms, in vitro experiments were performed using HepG2 and LX-2 cell lines as well as primary hepatocytes.Results\n\nNQO1 expression was markedly upregulated under cholestatic conditions. During the acute phase of DDC-induced injury, NKO mice demonstrated a protective phenotype, characterized by significantly reduced plasma ALT levels and less severe histological injury compared with WT controls. Histological analysis further revealed fewer TUNEL-positive hepatocytes and reduced fibrotic deposition in NKO mice. Transcriptomic profiling indicated that NQO1 ablation suppressed the epithelial-mesenchymal transition (EMT) and inflammation pathways, while enhancing bile acids and xenobiotic metabolism. Mechanistically, periostin was identified as a key upstream factor capable of inducing NQO1 expression and promoting intracellular reactive oxygen species (ROS) accumulation. Periostin-induced NQO1 protein expression was attenuated by both BAY 11-7082 and N-acetyl-L-cysteine. Notably, the disruption of NQO1 blunted periostin-driven oxidative stress. However, this protective effect is limited to the early phase of the disease and is not maintained during prolonged cholestatic injury.Conclusion\n\nNQO1 can function as a context-dependent regulator that exacerbates oxidative stress and fibrosis during the initial stages of PSC and suggests that targeting the periostin-NQO1 axis may offer therapeutic benefits.",
  "abstract_shown": true,
  "affiliations": [
    "Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, Korea",
    "Department of Biology and Microbiology, Changwon National University, Changwon, Korea"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Juhyun Kim"
    },
    {
      "affs": [
        0
      ],
      "name": "Seung Hee Woo"
    },
    {
      "affs": [
        0
      ],
      "name": "Da-Hyeun Yoon"
    },
    {
      "affs": [
        1
      ],
      "name": "Heedoo Lee"
    },
    {
      "affs": [
        0
      ],
      "name": "Chul-Ho Lee"
    },
    {
      "affs": [
        0
      ],
      "name": "Jung Hwan Hwang"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/9ty1q4axy9335.bib",
  "cited_by": 0,
  "doi": "10.1097/hc9.0000000000001076",
  "fulltext_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13694090/?tool=EBI",
  "id": "9ty1q4axy9335",
  "issns": [
    "2471-254X"
  ],
  "landing_url": "https://europepmc.org/article/PMC/PMC13694090",
  "language": "eng",
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2721|Liver Diseases and Immunity"
    ]
  ],
  "openalex": "W7224025506",
  "pdf_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13694090/pdf/?tool=EBI",
  "pmcid": "PMC13694090",
  "pmid": "42951873",
  "published": "2026-10-23",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/9ty1q4axy9335.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:20:00Z",
      "native_id": "PMC:PMC13694090",
      "source": "europepmc",
      "url": "https://europepmc.org/article/PMC/PMC13694090"
    },
    {
      "first_seen": "2026-10-31T00:20:34Z",
      "native_id": "MED:42951873",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42951873"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2721|Liver Diseases and Immunity",
      "subfield": "general"
    }
  ],
  "title": "NQO1 acts as a context-dependent regulator of oxidative stress and biliary fibrosis in primary sclerosing cholangitis",
  "title_text": "NQO1 acts as a context-dependent regulator of oxidative stress and biliary fibrosis in primary sclerosing cholangitis",
  "type": "peer-reviewed",
  "updated_at": "2026-10-31T00:20:34Z",
  "url": "https://research.draconitic.com/paper/9ty1q4axy9335",
  "venue": "Hepatology communications",
  "versions": []
}