Legumain promotes tubular ferroptosis by facilitating chaperone-mediated autophagy of GPX4 in AKI

摘要

LgmnWT and lgmnKO mice were randomized to 40 min of bilateral ischemia (n = 8). Kidney and serum samples were collected before and at day 1, 2, and 7 after IRI. A, B Renal functions assessed by serum creatinine (Cr) and BUN levels at the corresponding time points after IRI. *P < 0.05, **P < 0.01, ***P < 0.001 versus lgmnWT control; ♯P < 0.05, ♯♯P < 0.01 versus lgmnKO control; §P < 0.05, §§P < 0.01 versus lgmnWT after IRI at the corresponding time point. C, D Quantification of kidney KIM-1 and NGAL mRNA levels by qPCR. E Each pair of images includes a representative PAS-stained histologic photomicrograph of the kidney (top) from lgmnWT and lgmnKO mice on the indicated days after IRI and higher-magnification photomicrographs of the renal cortex (bottom; corresponding to the boxed area). Scale bar, 50 μm. F Quantification of histological renal damage. Tubular detachment, tubular dilation, and brush border damage were scored by the percentage area. G Histological ATN score. All data are expressed as the mean ± SD, *P < 0.05, ***P < 0.001; two-way ANOVA.