{
  "abstract": "Transforming growth factor-β1 (TGF-β1) is a key profibrotic mediator in diabetic kidney disease. Upstream stimulatory factor 1 (USF1) enhances TGF-β1 transcription through an E-box/glucose-response element in the TGF-β1 promoter under high-glucose conditions. We designed a sequence-specific pyrrole-imidazole (PI) polyamide targeting the human USF1-binding site in the TGF-β1 promoter and evaluated its activity in human renal mesangial cells (HRMCs). A target PI polyamide and a mismatch PI polyamide were synthesized. DNA binding and inhibition of the USF1-DNA interaction were assessed by gel mobility shift assays. HRMCs were exposed to high glucose with or without PI polyamides, and TGF-β1 and osteopontin expression were quantified by real-time PCR and Western blotting. The target PI polyamide bound the intended promoter sequence and reduced recombinant USF1 binding in vitro. In high-glucose-exposed HRMCs, the target PI polyamide suppressed TGF-β1 mRNA and protein expression, whereas the mismatch PI polyamide did not suppress TGF-β1 expression. The target PI polyamide also reduced osteopontin mRNA expression. These findings provide proof-of-concept that PI polyamide-mediated targeting of the human USF1-TGF-β1 axis can attenuate high-glucose-associated profibrotic responses in HRMCs.",
  "abstract_shown": true,
  "affiliations": [
    "Division of Nephrology, Hypertension, and Endocrinology, Department of Internal Medicine, Nihon University School of Medicine, 30-1 Oyaguchi Kami-chou, Itabashi-ku, Tokyo 173-8610, Japan.",
    "Division of Nephrology and Endocrinology, Ukima Chuo Hospital, Tokyo 115-0052, Japan."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 5,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Yurie Akiya"
    },
    {
      "affs": [
        0
      ],
      "name": "Hiroki Kobayashi",
      "orcid": "0000-0002-9674-0374"
    },
    {
      "affs": [
        0
      ],
      "name": "Akiko Tsunemi"
    },
    {
      "affs": [
        1
      ],
      "name": "Noboru Fukuda"
    },
    {
      "affs": [
        0
      ],
      "name": "Masanori Abe",
      "orcid": "0000-0002-9156-5415"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/fbxnc2bf8k4gg.bib",
  "cited_by": 0,
  "doi": "10.3390/cells15191818",
  "fulltext_url": "https://europepmc.org/articles/PMC13664332",
  "id": "fbxnc2bf8k4gg",
  "issns": [
    "2073-4409"
  ],
  "landing_url": "https://europepmc.org/article/MED/42882515",
  "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",
      "2727|Chronic Kidney Disease and Diabetes"
    ]
  ],
  "openalex": "W7220717825",
  "pdf_url": "https://europepmc.org/articles/PMC13664332?pdf=render",
  "pmcid": "PMC13664332",
  "pmid": "42882515",
  "published": "2026-10-06",
  "publisher": "MDPI AG",
  "ris": "https://research.draconitic.com/paper/fbxnc2bf8k4gg.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:00Z",
      "native_id": "MED:42882515",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42882515"
    },
    {
      "first_seen": "2026-10-30T12:19:02Z",
      "native_id": "10.3390/cells15191818",
      "source": "crossref",
      "url": "https://www.mdpi.com/2073-4409/15/19/1818"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "issn:2073-4409",
      "subfield": "cell-biology"
    }
  ],
  "title": "A Pyrrole-Imidazole Polyamide Targeting Human USF1 Binding Suppresses High Glucose-Induced TGF-β1 and Osteopontin Expression in Human Renal Mesangial Cells.",
  "title_text": "A Pyrrole-Imidazole Polyamide Targeting Human USF1 Binding Suppresses High Glucose-Induced TGF-β1 and Osteopontin Expression in Human Renal Mesangial Cells.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:19:02Z",
  "url": "https://research.draconitic.com/paper/fbxnc2bf8k4gg",
  "venue": "Cells",
  "versions": []
}