Figure 7. Renal tubule–specific knockout of Rest alleviates AKI through upregulating GCLM expression to inhibit ferroptosis.

Rest^RTKO mice and Rest^fl/fl mice were subjected to IRI and sacrificed on reperfusion day 1. Ferrostatin-1 (Fer-1; 5 mg/kg) or normal saline was intraperitoneally injected into the mice at the onset of reperfusion. The following indices were evaluated (n = 8 mice per group). (A) Representative immunohistochemical staining of 4-HNE from all groups. Scale bar: 50 μm. (B–D) TEM observation of mitochondria (B), representative Western blot analyses of GCLM and GPX4 (C), and GCL activity (D) of the kidneys from all groups. Scale bar: 1 μm (left); 0.15 μm (right). N, nucleus. Data are shown as mean ± SD and were analyzed by 1-way ANOVA (D). **P < 0.01; ***P < 0.001. NS, no significance.