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Abstract Acute kidney injury (AKI) stemming from sepsis, termed SA-AKI, frequently emerges as a predominant complication among critically ill patients, with over half of intensive care unit (ICU) AKI cases linked to sepsis. Ferroptosis in tubules is implicated in SA-AKI development, yet its regulatory mechanism remains unclear. Recently, C7ORF41, a conserved sequence on chromosome 7, was associated with inflammation and lipid accumulation in palmitic acid. We investigated C7ORF41's role in lipopolysaccharide (LPS) induced AKI models in C57BL mice. Post-LPS treatment, renal tubules showed reduced C7ORF41 expression. C7ORF41 deficiency significantly mitigated LPS induced lipid peroxidation, tissue damage, and renal dysfunction. In vitro experiments showed decreased ferroptotic cell death, lipid ROS, and GPX4 expression in renal tubular cells lacking C7ORF41. From a mechanistic standpoint, ferroptosis is facilitated by C7ORF41 through activating the pathway involving Keap1, Nrf2, and HO-1, known for its cytoprotective and antioxidant properties. Our findings suggest that C7ORF41 promotes ferroptosis in SA-AKI through Keap1/Nrf2/HO-1 Axis, highlighting its potential as a therapeutic target for SA-AKI treatment.
Yu et al. (Fri,) studied this question.
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