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acute-kidney-injury

Does blocking IRE1/JNK calm ferroptosis in AKI?

Liang Y, Liu Z, Qu L, et al. · Frontiers in pharmacology · 2022

Open access · cc by · source: Europe PMC

In I/R mice and H/R HK-2 cells, IRE1/JNK activation tracked with ferroptosis; inhibiting the pathway improved BUN/creatinine and ferroptosis markers.

Key findings

I/R caused abnormal renal function, tubular injury, IRE1/JNK activation, and ferroptosis; H/R cells showed ROS and ferroptotic mitochondria. IRE1/JNK inhibition lowered BUN/creatinine/injury and shifted ferroptosis markers; ferroptosis inhibition also attenuated IRE1/JNK.

Methodology

Modeled AKI with renal ischemia-reperfusion in 144 mice and hypoxia/reoxygenation in HK-2 cells, then inhibited IRE1/JNK or ferroptosis (e.g., Fer-1) to test cross-talk.

Limitations

Mouse/cell protection is not yet a clinical AKI therapy; timing, off-target effects, and human translation remain open.

How this study connects

Role on claims

Each row is a claim on a concept or method page where this paper supports, challenges, or qualifies the statement. Roles are hand-checked — not a model guess.

  • QualifiesFerroptosisconcept

    Triggering tumor ferroptosis can help checkpoint therapy in cold tumors (preclinical).

    In EGFR-mutant NSCLC models, cisplatin-driven tumor ferroptosis polarized N1 neutrophils and supported T-cell/Th1 programs that synergized with immune checkpoint inhibitor therapy.

    Scope note — renal protection restrains ferroptosis — opposite therapeutic direction from oncology induction

    Limits the claim's scope: a different population, assay, or outcome.

  • SupportsFerroptosisconcept

    Blocking IRE1/JNK can attenuate ferroptosis-linked renal I/R injury in mice/cells.

    Renal ischemia/reperfusion activated IRE1/JNK with ferroptotic tubular injury; inhibiting that axis improved BUN/creatinine and ferroptosis markers, aligning with ferrostatin-1-style protection.

    Evidence for the claim as stated.

  • SupportsFerroptosisconcept

    Cisplatin-induced ferroptosis aided ICI efficacy in cold tumors vs IRE1/JNK blockade reduced ferroptosis-linked kidney I/R injury

    Evidence for the claim as stated.

Open questions

Tensions this paper is part of

From concept pages' “where studies disagree.” Disagreement means the same question; scope means different assays, populations, or outcomes.

  • Scope difference — different assays, populations, or outcomes

    SupportsFerroptosis

    Cisplatin-induced ferroptosis aided ICI efficacy in cold tumors vs IRE1/JNK blockade reduced ferroptosis-linked kidney I/R injury

    Also on this tension

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Same topic cluster — not a recommendation engine.