MiR-34c-5p suppresses ferroptosis in ischemia/reperfusion-induced renal injury by targeting HSPA1B.

Renal ischemia/reperfusion (I/R) injury is a serious medical condition that causes acute kidney dysfunction and is associated with a high mortality rate. Ferroptosis is a form of nonapoptotic cell death marked by excessive lipid peroxidation. This study aimed to investigate the effect of miR-34c-5p/HSPA1B axis on ferroptosis in in hypoxia/reoxygenation (H/R)-stimulated human renal proximal tubular cells (HK-2) and I/R rat models. Erastin was employed to trigger ferroptosis, while Ferrostatin-1 was applied to suppress it. The viability of HK-2 cells was evaluated using cell counting kit-8 assays, whereas apoptosis was detected via TUNEL assays. The levels of mitochondrial superoxide, lipid reactive oxygen species (ROS), and iron concentration were measured as indicators of ferroptosis. Luciferase reporter assays and RNA pulldown assays were utilized to measure the binding relation between miR-34c-5p and HSPA1B. Hematoxylin-eosin staining of rat kidney tissues was performed to evaluate renal pathological changes. H/R treatment induced intracellular ferroptosis, and the inhibition of ferroptosis via Ferrostatin-1 attenuated H/R-induced cell injury. HSPA1B was upregulated in the established cell model and promoted intracellular ferroptosis. MiR-34c-5p targeted HSPA1B in HK-2 cells, leading to a reduction in intracellular ROS production, Fe(2+) level, and the rate of apoptosis. Importantly, miR-34c-5p mitigated renal histological damage mediated by I/R injury through the suppression of ferroptosis. In conclusion, miR-34c-5p inhibits ferroptosis in renal I/R injury by targeting HSPA1B. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10616-026-00933-9.