Arfgef3 knockout ameliorates ischemia reperfusion-induced acute kidney injury via mitochondrial dysfunction alleviation in mice.

Ischemia reperfusion-induced acute kidney injury (IRI-AKI) is a prevalent clinical complication among hospitalized patients with high morbidity and mortality. Mitochondria, as crucial organelles for maintaining cellular homeostasis, play a pivotal role in IRI-AKI pathogenesis. Currently, no effective and definitive therapeutic targets have been established for IRI-AKI treatment. Previous sequencing data analysis revealed significant upregulation of Arfgef3 following renal ischemia-reperfusion injury, suggesting its potential as a therapeutic target. This study demonstrates that Arfgef3 expression is markedly elevated after ischemia reperfusion injury. Furthermore, Arfgef3 knockout (KO) significantly ameliorated renal injury induced by ischemia-reperfusion in mice. In addition, Arfgef3 knockout effectively attenuates renal inflammation (IL6, MCP1, TNF-α), oxidative stress and apoptosis levels. In addition, Arfgef3 knockout substantially improves ischemia reperfusion-induced mitochondrial abnormalities including mitochondrial biogenesis markers and ATP production capacity. In conclusion, Arfgef3 participates in IRI-AKI pathogenesis by regulating mitochondrial function. Arfgef3 knockout confers renal protection through improving mitochondrial dysfunction, thereby reducing inflammatory response, oxidative stress and apoptosis. These findings provide novel insights into IRI-AKI mechanisms and highlight Arfgef3 as a potential therapeutic target.