{
  "abstract": "Obstructive nephropathy is a significant and preventable contributor to chronic kidney disease, yet no disease-modifying antifibrotic agents are currently available. We hypothesized that interferon regulatory factor 5 (IRF5) functions as a macrophage transcriptional regulator that directly transactivates matrix metalloproteinase 9 (MMP9) to initiate early extracellular matrix (ECM) remodeling. Analysis of 30 human obstructive nephropathy biopsy specimens demonstrated that IRF5+CD68+ macrophage density increased progressively with fibrosis severity and correlated significantly with α-smooth muscle actin–positive (α-SMA+) areas. In the murine unilateral ureteral obstruction (UUO) model, both global and myeloid-specific Irf5 deletion significantly attenuated collagen deposition, immune cell infiltration, and fibrotic gene expression compared with WT controls. Cleavage under targets and tagmentation (CUT&Tag) analysis demonstrated that IRF5 directly binds the Mmp9 enhancer region and increases chromatin accessibility. Consequently, myeloid-specific Irf5 KO significantly reduced Mmp9 mRNA and MMP9 protein levels. Pharmacological inhibition using the IRF5 inhibitor N5-1 mitigated established fibrosis, downregulated α-SMA and MMP9 expression, and reduced CD68+ macrophage infiltration. These findings identify the IRF5/MMP9 axis as a therapeutically targetable pathway driving macrophage-mediated ECM expansion and provide preclinical evidence supporting IRF5 inhibition as a potential treatment strategy for patients with obstructive nephropathy.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Urology and",
    "Department of Pathology, Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, China.",
    "Department of Cardiology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.",
    "Department of cardiovascular surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 9,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Jia Wei"
    },
    {
      "affs": [
        0
      ],
      "name": "Gengyu Du"
    },
    {
      "affs": [
        0
      ],
      "name": "Zixia Li"
    },
    {
      "affs": [
        1
      ],
      "name": "Min Yang"
    },
    {
      "affs": [
        0
      ],
      "name": "Ting Chen"
    },
    {
      "affs": [
        0
      ],
      "name": "Zihao Xu"
    },
    {
      "affs": [
        2
      ],
      "name": "Zhen Yuan"
    },
    {
      "affs": [
        3
      ],
      "name": "Yidan Zheng"
    },
    {
      "affs": [
        0
      ],
      "name": "Xiang Yan"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/bwc6bpbx3e4sv.bib",
  "cited_by": 0,
  "doi": "10.1172/jci.insight.201877",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13726410/",
  "id": "bwc6bpbx3e4sv",
  "issns": [
    "2379-3708"
  ],
  "landing_url": "https://doi.org/10.1172/jci.insight.201877",
  "language": "en",
  "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": [
    [
      "heading",
      "Research Article"
    ],
    [
      "openalex",
      "2727|Chronic Kidney Disease and Diabetes"
    ]
  ],
  "openalex": "W7196999804",
  "pdf_url": null,
  "pmcid": "PMC13726410",
  "pmid": "42560765",
  "published": "2026-08-06",
  "publisher": "American Society for Clinical Investigation",
  "ris": "https://research.draconitic.com/paper/bwc6bpbx3e4sv.ris",
  "sources": [
    {
      "first_seen": "2026-11-05T12:22:46Z",
      "native_id": "PMC13726410",
      "source": "pmc",
      "url": "https://doi.org/10.1172/jci.insight.201877"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2727|Chronic Kidney Disease and Diabetes",
      "subfield": "general"
    }
  ],
  "title": "Interferon regulatory factor 5 in myeloid cells promotes obstructive nephropathy-induced renal fibrosis in vivo",
  "title_text": "Interferon regulatory factor 5 in myeloid cells promotes obstructive nephropathy-induced renal fibrosis in vivo",
  "type": "peer-reviewed",
  "updated_at": "2026-11-05T12:22:46Z",
  "url": "https://research.draconitic.com/paper/bwc6bpbx3e4sv",
  "venue": "JCI Insight",
  "versions": []
}