Inhibition of sepsis-induced acute kidney injury via the circITCH-miR-579-3p-ZEB2 axis

Circular RNAs (circRNAs) are linked to the regulation of sepsis-induced acute kidney injury (AKI). However, the function of circITCH in the development of sepsis-induced AKI is still unclear. The levels of circITCH, miR-579-3p and ZEB2 were examined by real-time PCR and immunoblotting. Then, the roles of circITCH in cell viability, apoptosis, and inflammation in lipopolysaccharide (LPS)-treated HK-2 cells were evaluated. The further mechanism was investigated using rescue assays. CircITCH was downregulated in septic AKI patients and LPS-triggered HK-2 cells. CircITCH overexpression restored cell viability in LPS-treated HK-2 cells and restrained apoptosis and inflammatory cytokine production. CircITCH negatively regulated miR-579-3p, thereby upregulating ZEB2 expression. Taken together, circITCH alleviates LPS-induced HK-2 cell injury by regulating miR-579-3p/ZEB2 signal axis, which provides a theoretical basis for AKI therapy.

Automated summary

This study found that circular RNAs (circRNAs) are associated with the regulation of sepsis-induced acute kidney injury (AKI), but the specific function of circITCH in the development of sepsis-induced AKI is still unclear. The levels of circITCH, miR-579-3p, and ZEB2 were examined, and the roles of circITCH in cell viability, apoptosis, and inflammation were evaluated in LPS-treated HK-2 cells. CircITCH overexpression restored cell viability, inhibited apoptosis and inflammatory cytokine production in LPS-treated HK-2 cells by negatively regulating miR-579-3p and upregulating ZEB2 expression. This study provides a theoretical basis for AKI therapy by demonstrating the protective role of circITCH in LPS-induced HK-2 cell injury.