{
  "abstract": "Ischemia–reperfusion injury (IRI) causes acute kidney injury (AKI) and transplant dysfunction. NKG2D ligands (human MICA and murine RAE-1/H60) drive immune activation, while Roxadustat (FG-4592) is reportedly renoprotective. We hypothesized that Roxadustat modulates these ligands in renal IRI. MICA expression was assessed in biopsies from AKI and post-renal transplantation (PRT) patients versus controls. Male Balb/c mice received Roxadustat or vehicle before unilateral IRI, followed by assessment of kidney injury and HIF-1α, RAE-1, and H60 expression. In vitro, human and murine tubular cells underwent hypoxia/reoxygenation with or without FG-4592 pretreatment, and ligand expression was analyzed. Our results showed that MICA expression was elevated in kidney tissues from individuals with AKI or PRT compared with controls. In mice, FG-4592 pretreatment attenuated renal IRI-induced dysfunction and tubular injury, concurrently stabilizing HIF-1α protein levels. Notably, FG-4592 treatment enhanced the expression of murine NKG2D ligands at the transcriptional and translational levels in renal IRI. This effect was corroborated in vitro, where hypoxia/reoxygenation upregulated MICA in human and RAE-1 in mouse tubular cells, a response potentiated by FG-4592. In conclusion, Roxadustat protects against renal IRI but upregulates NKG2D ligands, warranting further study of its mechanisms and consequences in AKI/PRT.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Nephrology, Huashan Hospital, Fudan University, Shanghai 200040, China",
    "Department of Nephrology, Qilu Hospital (Qingdao), Shandong University, Qingdao 266035, China",
    "Department of Pharmacy, Huashan Hospital, Fudan University, Shanghai 200040, China",
    "Department of Pharmacy, Tongji Hospital, Tongji University, Shanghai 200065, China"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 8,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Huan Yang"
    },
    {
      "affs": [
        0
      ],
      "name": "Ningxin Xu"
    },
    {
      "affs": [
        0
      ],
      "name": "Yong Wu"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Ming Cheng"
    },
    {
      "affs": [
        2,
        3
      ],
      "name": "Xiaoyan Qiu"
    },
    {
      "affs": [
        0
      ],
      "name": "Shaojun Liu",
      "orcid": "0000-0003-2433-8340"
    },
    {
      "affs": [
        0
      ],
      "name": "Ming Zhang"
    },
    {
      "affs": [
        0
      ],
      "name": "Minmin Zhang"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/4qcfxpgyc3fmt.bib",
  "cited_by": 0,
  "doi": "10.3390/biom16101437",
  "fulltext_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13702372/?tool=EBI",
  "id": "4qcfxpgyc3fmt",
  "issns": [
    "2218-273X"
  ],
  "landing_url": "https://www.mdpi.com/2218-273X/16/10/1437",
  "language": "eng",
  "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": [
    [
      "openalex",
      "2727|Acute Kidney Injury Research"
    ]
  ],
  "openalex": "W7216256218",
  "pdf_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13702372/pdf/?tool=EBI",
  "pmcid": "PMC13702372",
  "pmid": null,
  "published": "2026-10-01",
  "publisher": "MDPI AG",
  "ris": "https://research.draconitic.com/paper/4qcfxpgyc3fmt.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:59Z",
      "native_id": "10.3390/biom16101437",
      "source": "crossref",
      "url": "https://www.mdpi.com/2218-273X/16/10/1437"
    },
    {
      "first_seen": "2026-10-30T12:21:48Z",
      "native_id": "PMC:PMC13702372",
      "source": "europepmc",
      "url": "https://europepmc.org/article/PMC/PMC13702372"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2727|Acute Kidney Injury Research",
      "subfield": "general"
    }
  ],
  "title": "Roxadustat (FG-4592) Attenuates Renal Ischemia–Reperfusion Injury but Upregulates the NKG2D Ligand MICA",
  "title_text": "Roxadustat (FG-4592) Attenuates Renal Ischemia–Reperfusion Injury but Upregulates the NKG2D Ligand MICA",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:21:48Z",
  "url": "https://research.draconitic.com/paper/4qcfxpgyc3fmt",
  "venue": "Biomolecules",
  "versions": []
}