GPX3 alleviated ischemia-reperfusion inflammatory injury in kidney transplantation by inhibiting pyroptosis of renal tubular epithelial cells
10.12464/j.issn.1674-7445.2026113
- VernacularTitle:GPX3通过抑制肾小管上皮细胞焦亡减轻肾移植缺血-再灌注炎症损伤
- Author:
Jun PEI
1
;
Moudong WU
1
;
Jinpu PENG
1
;
Hongyu TANG
1
;
Nini AN
1
;
Xingyu PAN
2
Author Information
1. Department of Pediatric Surgery, Guizhou Provincial People's Hospital, Guiyang 550002, China.
2. null.
- Publication Type:OriginalArticle
- Keywords:
Glutathione peroxidase 3;
Kidney transplantation;
Ischemia-reperfusion injury;
Selenium protein;
Pyroptosis;
Inflammatory response;
Acute kidney injury;
Pathological injury score
- From:
Organ Transplantation
2026;17(6):963-971
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the role and potential mechanism of glutathione peroxidase (GPX)3 in ischemia-reperfusion inflammatory injury of renal transplantation. Methods Based on the dataset GSE30718, gene set enrichment analysis (GSEA) was used to explore the potential biological processes (BP) changes and mechanisms of acute kidney injury (AKI) in renal transplantation. C57BL/6 mice were divided into 3 groups according to the intervention conditions: sham group (Sham group), kidney transplantation group (KT group) and kidney transplantation + GPX3 overexpression group (KT + GPX3 group). In the KT + GPX3 group, GPX3 adenovirus was injected via the tail vein to intervene the donor mice, while the Sham group and KT group were intervened with the same dose of empty vector virus. Then, the kidney transplantation model was constructed. At 24 hours after model establishment, the blood from the inferior vena cava of mice was collected to detect blood urea nitrogen (BUN) and serum creatinine (Scr). Immunofluorescence staining was used to detect the levels of GPX3, NOD-like receptor protein 3 (NLRP3), Cleaved-caspase D (GSDMD), interleukin (IL)-6, IL-1β and reactive oxygen species (ROS) in mouse renal tissues. Western blotting was used to detect the levels of GPX3, neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule 1 (KIM-1), NLRP3, Cleaved-GSDMD, IL-6 and IL-1β in mouse renal tissues. Hematoxylin-eosin staining was used to evaluate the degree of renal tissue pathological damage. Transcriptional sequencing was performed on mouse renal tissues to analyze the differentially expressed genes and potential BP. Results GSEA results showed that BP related to the regulation of inflammatory response, pyroptosis and glutathione metabolism were activated during kidney transplant IRI, and the mechanisms of inflammatory-related pathways and GSH metabolism were activated. Compared with the Sham group, the protein level of GPX3 was decreased in the KT group, and the degree of renal tissue pathological damage was aggravated, with an increased pathological damage score, and the expression levels of Scr and BUN, NGAL and KIM-1 were increased; compared with the KT group, the protein level of GPX3 was increased in the KT + GPX3 group, the degree of renal tissue pathological damage was reduced, the pathological damage score was decreased, and the expression levels of Scr and BUN, NGAL and KIM-1 were decreased (all P < 0.05). Transcriptional sequencing results showed that after overexpression of GPX3, BP related to the regulation of inflammatory response and pyroptosis were enriched. Further experiments proved that compared with the Sham group, the levels of NLRP3, Cleaved-GSDMD, ROS, IL-6 and IL-1β were increased in the KT group; compared with the KT group, the levels of NLRP3, Cleaved-GSDMD, ROS, IL-6 and IL-1β were decreased in the KT + GPX3 group (all P < 0.05). Conclusions GPX3 may alleviate renal transplant ischemia-reperfusion inflammatory injury by inhibiting pyroptosis.
