{
  "abstract": "Hypoxia-inducible factor (HIF) plays a central role in the cellular response to hypoxia and is negatively regulated under normoxic conditions by prolyl hydroxylase domain-containing proteins (PHDs), also referred to as HIF prolyl hydroxylases (HIF-PHs). HIF-PH inhibitors induce erythropoietin (EPO) expression by activating HIF and are widely used for the treatment of renal anemia; however, their effects on intraocular vascular endothelial growth factor (VEGF) expression remain unclear. In this study, we examined the effects of all five HIF-PH inhibitors (roxadustat, daprodustat, vadadustat, enarodustat, and molidustat) on Vegfa expression in the retina in mice. C57BL/6 J mice were orally administered each inhibitor. Six hours after administration, the kidney, retina, and liver were collected, and transcription levels were quantified by real-time reverse transcription PCR (real-time RT-PCR). Renal Epo transcription was significantly increased by molidustat (P < 0.01), roxadustat (P < 0.01), and enarodustat (P < 0.05) significantly increased renal Epo transcription. Retinal Vegfa transcription was significantly increased by four inhibitors (P < 0.01), with molidustat showing no significant effect. In the liver, Vegfa transcription was increased by daprodustat (P < 0.05) and vadadustat (P < 0.01). No significant correlation was observed between renal Epo and retinal Vegfa transcription levels for any of the HIF-PH inhibitors. These findings indicate that HIF-PH inhibitors differentially regulate hypoxia-responsive genes across tissues and suggest that their potential effects on retinal Vegfa transcription should be considered when evaluating their ocular safety.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": null,
  "arxiv": null,
  "author_total": 5,
  "authors": [
    {
      "name": "Junki Hoshino",
      "orcid": "0009-0001-9389-276X"
    },
    {
      "name": "Kazuki Irie",
      "orcid": "0000-0002-7553-6948"
    },
    {
      "name": "Akimitsu Konishi",
      "orcid": "0000-0002-3291-0821"
    },
    {
      "name": "Hideo Akiyama",
      "orcid": "0000-0001-6272-9911"
    },
    {
      "name": "Yoji Andrew Minamishima",
      "orcid": "0000-0001-7995-9318"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/ccmj769bdb7yh.bib",
  "cited_by": 0,
  "doi": "10.1038/s41598-026-73839-3",
  "fulltext_url": "https://doi.org/10.1038/s41598-026-73839-3",
  "id": "ccmj769bdb7yh",
  "issns": [
    "2045-2322"
  ],
  "landing_url": "https://www.nature.com/articles/s41598-026-73839-3",
  "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": [
    [
      "lcc",
      "Q"
    ],
    [
      "lcc",
      "R"
    ],
    [
      "openalex",
      "2720|Erythropoietin and Anemia Treatment"
    ]
  ],
  "openalex": "W7223178173",
  "pdf_url": "https://www.nature.com/articles/s41598-026-73839-3.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-22",
  "publisher": "Springer Science and Business Media LLC",
  "ris": "https://research.draconitic.com/paper/ccmj769bdb7yh.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:33Z",
      "native_id": "10.1038/s41598-026-73839-3",
      "source": "crossref",
      "url": "https://www.nature.com/articles/s41598-026-73839-3"
    },
    {
      "first_seen": "2026-10-30T13:45:53Z",
      "native_id": "4c96326ed4744fa49486c5e67978d9d8",
      "source": "doaj",
      "url": "https://doi.org/10.1038/s41598-026-73839-3"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2720|Erythropoietin and Anemia Treatment",
      "subfield": "general"
    }
  ],
  "title": "Effects of clinically available HIF-PH inhibitors on retinal Vegfa transcription",
  "title_text": "Effects of clinically available HIF-PH inhibitors on retinal Vegfa transcription",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T13:45:53Z",
  "url": "https://research.draconitic.com/paper/ccmj769bdb7yh",
  "venue": "Scientific Reports",
  "versions": []
}