SUMO1 alleviates renal ischemia-reperfusion injury in neonatal mice by modulating apoptosis and ferroptosis

In this research, we examined the regulatory mechanism of small ubiquitin-related modifiers (SUMOs) in the context of acute kidney injury (AKI) induced by renal ischemia-reperfusion injury (IRI). We systematically evaluated the biological function of SUMOylation in the pathological process of IRI by establishing a SUMO1 knockout (SUMO1^−/−) mouse model. One-week-old male and female SUMO1^−/− mice, along with their wild-type (WT) littermate controls, were employed to establish a 20-min renal ischemia model through unilateral renal artery clamping. Renal tissue specimens were harvested at 48-h post-reperfusion, and multidimensional analyses were performed by histopathological assessment, molecular biology testing, and primary cell validation. Compared to the WT controls, kidneys of SUMO1^−/− mice exhibited more pronounced AKI pathological features post-IRI, including typical injury phenotypes such as increased vacuolization of renal tubular epithelial cells. At the level of molecular mechanisms, the absence of SUMO1 markedly increased the expression of tumor necrosis factor-<italic>α</italic> (TNF-<italic>α</italic>). Notably, the SUMO1^−/− group showed increased renal ferritin deposition and increased severity of apoptosis compared with the WT group, suggesting that the lack of SUMOylation exacerbates the process of IRI-induced ferroptosis and programmed cell death. These systematic findings confirm that SUMOylation has an important cytoprotective function during renal IRI, and its mechanism of action may involve multiple pathways such as regulating inflammatory response, maintaining iron metabolic homeostasis, and inhibiting apoptosis.