ArticleCell death & disease2026
USAG-1 aggravates renal ischemia‒reperfusion injury via promoting GPX4 degradation-induced ferroptosis.
Article in Cell death & disease, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
0 citing papers in PubMed.
No citing paper in PubMed yet.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors.
Funding
Abstract
Renal ischemia‒reperfusion injury (IRI) remains an inevitable complication in kidney transplantation and a leading cause of delayed graft function (DGF). Ferroptosis, a form of iron-dependent lipid peroxidation-driven cell death, has emerged as an important mechanism contributing to renal IRI. Although uterine sensitization-associated gene-1 (USAG-1) has been implicated in both acute and chronic kidney injury, its involvement in IRI-associated ferroptosis has not been elucidated. In this study, using murine renal ischemia-reperfusion models and human transplant kidney biopsies (from donation after circulatory death donors), we demonstrate that USAG-1 is significantly upregulated under ischemic stress. Importantly, higher USAG-1 expression in donor kidneys was associated with worse allograft function post-transplantation, suggesting that USAG-1 may serve as a promising biomarker for transplant injury and outcomes. In addition, genetic ablation of USAG-1 markedly attenuated both IRI- and folic acid-induced ferroptosis, accompanied by reduced acute kidney injury severity. Mechanistically, glutathione peroxidase 4 (GPX4) was a critical downstream effector of USAG-1 in mediating ferroptotic processes. HSP family A member 5 (HSPA5), a canonical molecular chaperone, stabilized GPX4 via direct interactions. Our findings revealed that overexpressed USAG-1 competitively binds to HSPA5, thereby disrupting the HSPA5-GPX4 interaction. This interference was abrogated by truncation mutants of USAG-1 that failed to interact with HSPA5. Notably, functional validation of the USAG-1/HSPA5/GPX4 axis confirmed that preserving HSPA5-GPX4 binding mitigated ferroptosis and alleviated renal injury. Overall, our study reveals a previously unrecognized mechanism by which USAG-1 promotes ferroptosis in renal IRI and highlights the therapeutic potential of targeting the USAG-1/HSPA5/GPX4 axis to improve graft outcomes post-transplantation.
Indexed as
Identifiers
What Socratic holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.