CHMP2B exacerbates renal tubular injury in sepsis-induced acute kidney injury by enhancing autophagy blockade.

Sepsis-induced acute kidney injury (SI-AKI) increases the mortality rate of critically ill patients, but its pathophysiological mechanisms remain incompletely understood. Autophagy has been shown to be involved in the process of SI-AKI. Bioinformatics analysis of the GSE256430 dataset indicates that CHMP2B is upregulated in SI-AKI. However, the impact and specific mechanisms of CHMP2B on SI-AKI are still unknown. In this study, a mouse model induced by cecal ligation and puncture and lipopolysaccharide-simulated HK-2 cells were established to simulate SI-AKI. The results confirmed that CHMP2B was significantly upregulated and autophagy was blocked in both SI-AKI mouse and cell models. Knockdown of CHMP2B alleviated renal function decline and renal tubular tissue damage in SI-AKI mice. In SI-AKI cell models, autophagy activators led to reduced apoptosis and increased viability of renal tubular epithelial cells. Furthermore, the reduction in apoptosis, increase in autophagy, and enhancement in cell viability mediated by CHMP2B knockdown were counteracted by autophagy inhibitors. Therefore, CHMP2B participated in the progression of SI-AKI by inhibiting autophagy in renal tubular epithelial cells. Mechanistically, it was revealed that upregulated transcription factor USF1 promoted CHMP2B expression, thereby inducing autophagy blockade in SI-AKI. In summary, CHMP2B-mediated autophagy blockade exacerbated renal tubular injury, promoting SI-AKI development. These findings provide new insights into understanding the pathological mechanisms of SI-AKI and developing strategies to treat it by modulating autophagy.