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Peer-reviewedCC BY 4.0Biomolecules

Roxadustat (FG-4592) Attenuates Renal Ischemia–Reperfusion Injury but Upregulates the NKG2D Ligand MICA

  • Huan Yang1
  • Ningxin Xu1
  • Yong Wu1
  • Ming Cheng1,2
  • Xiaoyan Qiu3,4
  • Shaojun Liu1
  • Ming Zhang1
  • Minmin Zhang1
4 affiliations
  1. 1Department of Nephrology, Huashan Hospital, Fudan University, Shanghai 200040, China
  2. 2Department of Nephrology, Qilu Hospital (Qingdao), Shandong University, Qingdao 266035, China
  3. 3Department of Pharmacy, Huashan Hospital, Fudan University, Shanghai 200040, China
  4. 4Department of Pharmacy, Tongji Hospital, Tongji University, Shanghai 200065, China
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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.

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Cite

BibTeXRIS
BibTeX
@article{yang2026roxadustat,
  title = {{Roxadustat (FG-4592) Attenuates Renal Ischemia–Reperfusion Injury but Upregulates the NKG2D Ligand MICA}},
  author = {Huan Yang and Ningxin Xu and Yong Wu and Ming Cheng and Xiaoyan Qiu and Shaojun Liu and Ming Zhang and Minmin Zhang},
  journal = {Biomolecules},
  year = {2026},
  month = oct,
  doi = {10.3390/biom16101437},
  url = {https://www.mdpi.com/2218-273X/16/10/1437},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Roxadustat (FG-4592) Attenuates Renal Ischemia–Reperfusion Injury but Upregulates the NKG2D Ligand MICA
AU  - Huan Yang
AU  - Ningxin Xu
AU  - Yong Wu
AU  - Ming Cheng
AU  - Xiaoyan Qiu
AU  - Shaojun Liu
AU  - Ming Zhang
AU  - Minmin Zhang
PY  - 2026
DA  - 2026/10/01
JO  - Biomolecules
DO  - 10.3390/biom16101437
UR  - https://www.mdpi.com/2218-273X/16/10/1437
AB  - 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.
SN  - 2218-273X
ER  -